Surgery Vol 1 2021 Cairo University PDF

Chapter 4: Acute Haemorrhage and Blood Transfusion CHAPTER4 ACUTE HAEMORRHAGE AND BLOOD TRANSFUSION CHAPTER CONTENTS Classification of haemorrhage Acute haemorrhage causes loss of both circulating blood volume and oxygen carrying capacity. The common causes include penetrating and blunt trauma, g...

Chapter 4: Acute Haemorrhage and Blood Transfusion CHAPTER4 ACUTE HAEMORRHAGE AND BLOOD TRANSFUSION CHAPTER CONTENTS Classification of haemorrhage Acute haemorrhage causes loss of both circulating blood volume and oxygen carrying capacity. The common causes include penetrating and blunt trauma, gastrointestinal bleeding, and obstetrical bleeding. Haemorrhage may be classified according to Site • External. Bleeding is visible as it occurs through skin wounds or from a body orifice as in epistaxis. • Internal o In body cavities, e.g., haemoperitoneum and haemothorax. o Interstitial, e.g., fracture haematoma. Type of disrupted vessel • Arterial. Blood is bright red and comes in pulsatile jets. • Venous. Blood is dark red and comes in a steady flow. • Capillary. Bleeding occurs as diffuse ooze of bright red blood. Timing in relation to trauma: • Classification of haemorrhage • Pathophysiological response to haemorrhage • Clinical picture of haemorrhage • Treatment of haemorrhage • Blood transfusion o Collection & storage of blood o Blood products o Possible complications o Alternatives to homologous blood transfusion Haemorrhage is classified according to: • Site: External or internal. • Type of disrupted vessel: Arterial, venous or capillary. • Timing: Primary, reactionary or secondary. • Aetiology: Traumatic, pathological or spontaneous. Common causes of severe haemorrhage: • Trauma: Splenic or liver injury, haemothorax, pelvis fracture • Major surgery • Bleeding oesophageal varices • Bleeding duodenal ulcer • Ruptured aortic aneurysm • Pre and postpartum haemorrhage Ruptured ectopic pregnancy. Body response aims to: • Stop bleeding • Maintain effective blood volume. This response is based on neural and endocrinal mechanisms. • Primary haemorrhage occurs at the time of trauma. • Reactionary haemorrhage occurs within 24 hours after trauma. As the blood pressure rises due to correction of hypovolaemia, an insecure ligature slips or a clot is dislodged. • Secondary haemorrhage occurs one to two weeks after trauma due to infection eroding a vessel wall, e.g. after haemorrhoidectomy. It can be fatal if a large artery is involved, e.g., the carotid after sloughing of the skin flaps of a radical neck dissection. Aetiology • Traumatic, which might be accidental or iatrogenic. • Pathological o Atherosclerotic, e.g., ruptured aortic aneurysm. o Inflammatory, e.g., bleeding peptic ulcer. liJIII General Surgery Hemorrhage Definition: Escape of RBCs outside the vessles, or organs Classification: Site 1. External: wounds or epistaxis or haematemesis. 2. Internal: a. In body cavities, e.g., haemoperitoneum and haemothorax. b. Interstitial, e.g., fracture haematoma. Type of vessel 1. Arterial. Blood is bright red and comes in pulsatile jets. 2. Venous. Blood is dark red and comes in a steady flow. 3. capillary. Bleeding occurs as diffuse ooze of bright red blood. Timing: 1. Primary haemorrhage occurs at the time of trauma. 2. Reactionary haemorrhage - Occurs within 24 hours after trauma . - Due to an insecure ligature slips or a clot is dislodged. 3. Secondary haemorrhage - 1- 2 weeks after trauma, due to infection eroding a vessel wall - It can be fatal if a large artery is involved. Aetiology 1. Traumatic  Accidental.  Surgical.  lnterventional procedures, e.g. percutaneous transhepatic cholangiography (PTC). 2. Pathological  Atherosclerotic (ruptured aortic aneurysm) .  Inflammatory (bleeding peptic ulcer).  Neoplastic (haematuria In renal cancer}. 3. Bleeding diathesis can increase the amount of traumatic and pathological bleeding, or cause bleeding with little or no trauma (spontaneous haemorrhage). 28 General Surgery Physiological response to hemorrhage: Locally: Stopping the bleeding - Vasoconstriction and retraction of the intima of the injured vessel. - Platelet plug. - Blood clotting. They are more effective when the vessel is completely transected than when there is a side tear, and in traumatic than in pathological cases. Systemically: A. Neural factors. ↓ stimulation of arterial baroreceptors (aortic arch and carotid sinus) and atrial stretch receptors → Inhibition of the normal inhibitory discharge in the vagus and glossopharyngeal nerves on the vasomotor centre  stimulation of the sympathetic system.  The effects include: 1. Constriction of veins: - Normally contain two-thirds of the blood volume - Displaces blood from the periphery into the heart. 2. Constriction of arterioles - Involves mainly the arterioles of the skin, skeletal muscle, and splanchnic area  Raises the peripheral resistance. 3. Increased rate and strength of cardiac contraction. Maintaining effective circulatory volume and perfusion of critical tissues (brain and heart). at the expense of less critical tissues (skin, skeletal muscle and splanchnic area). B. Endocrine factors 1 Catecholamine: ↑heart rate and myocardial contraction and cause constriction of them arterioles of the skin, kidney and viscera. 2 The metabolic hormones  ↑ACTH, cortisol, growth hormone and glucagon.  Insulin release is inhibited by adrenaline and noradrenaline. 29 General Surgery 3 The renin-angiotensin aldosterone system. - Renin secreted in response to renal hypoperfusion. - Renin splits angiotensinogen to angiotensin I - Which is converted to angiotensin II by a converting enzyme in the lung. - Angiotensin II is a powerful vasoconstrictor and sodium and water retention by the kidney as well as release of aldosterone. 4 ADH (vasopressin). C. Transcapillary refill.  ↓blood volume and constriction of arterioles  drops the capillary hydrostatic pressure and promotes movement of fluid from the interstitium into the capillaries.  The resulting haemodilution increases the blood volume and lowers its viscosity, thus improving effective circulatory volume. N.B - This Mechanism can compensate for losses up to 15% of blood volume only. - Blood volume is estimated as 70 ml/kg in adults, 80ml/kg in children. - i.e in adult : 15% from 5 Liters = 750 cc - in neonate: 10 % from 280 cc = 28 cc Clinical Picture Symptoms 1 Weakness and fainting especially when standing. 2 The patient feels cold and thirsty. Signs 1 Mental status: vary from anxious to drowsy.. 2 Pulse and blood Pressure. - Mild loss (< 500 ml): Pulse and B.P may remain normal. - More loss: Tachycardia but the blood pressure remains stable. - Further loss: Hypotension develops. 3 Respiratory rate· Tachypnea and air hunger. 4 Temperature.  Hypothermia 5 Skin: Pale, cold (vasoconstriction) and clammy with slow capillary refill. 6 Oliguria results due to diminished renal perfusion. 30 General Surgery Estimating blood loss  Blood volume is estimated as 70 mi/Kg in adults and 80 mi/Kg in children. 1. Clinical data Blood loss Mental status Skin Capillary refill Blood pressure -systolic -diastolic -pulse pressure Respiratory rate Urine (ml/h) 2. Class II 15-30% (750-1500 ml) Aggressive to-drowsy. Pale and cold >2 sec. Class III Class IV 30-40% >40% (1500-2000ml) (>2000ml) Anxious Drowsy restless. to unconscious Pale and colder. Pale and very cold >2 sec. >2 sec. undetectable. Normal Normal Normal 14-20 >30 Normal(supine) Raised Low 20-30 20-30 Low Low low 30-35 10-20 Low Low low >35 0-10 Type of injury.    3. Class I Up to 15% (750ml) Normal to anxious) Normal Normal Haematoma around a fracture of the tibia may contain 500-1500 ml of blood. Fractured shaft of femur, soo-2000 ml; Fractured pelvis, 2000-3000 mi. Blood loss at operation  Sum of the suction reservoir and the amount mopped up by the swabs. 31 General Surgery Management of Hemorrhage Stop hemorrhage.     (Packing, Pressure, Position) The wound is covered by a dressing And pressure is applied manually, or by a sphygmomanometer cuff. o Tourniquets are contraindicated. Elevation of the limb above the heart (decreases arterial bleeding). Other examples: o Anti-shock garment (PASG), o Balloon tamponade from oesophageal varices. Restore blood volume. Class II     The deficit is estimated at 15-30% {750-1500 ml/70 kg). The replacement solution is lactated Ringer's. The amount is 3 times the estimated deficit (3:1). Administration. o Two liters are given as a bolus. o If there is definite improvement: the remaining litre is given more slowly followed by the maintenance requirements and continued observations o Haematocrit <30 requires blood transfusion. o If there is moderate improvement. the possibilities are:  inadequate replacement.  Cardiac tamponade and tension pneumothorax.  Blood transfusion is started if bleeding is still active. Class III and IV     Management as class II till blood transfusion. Plasma expander can be used until blood is available. The volume of transfused blood equal the estimated deficit (1:1). Failure to improve and a rising OJP indicate: o Tension pneumothorax, Cardiac tamponade, Cardiac failure. o Major thoracic, abdominal, or pelvic injury. 32 General Surgery Optimize oxygen delivery.    40% oxygen is given for class II haemorrhage 100% for classes Ill and IY. Mechanical ventilation can be used to improve oxygen delivery. General care of the patient.   Bed rest and analgesia (morphia, 3-5 mg IV). Morphine: contraindicated in head injury and in respiratory insufficiency. Monitoring:      Foley's catheter. Vital signs. C.B.C: haematocrits ECG for early detection of shock-induced arrhythmias. Invasive Monitoring: - Central venous pressure - A pulmonary artery catheter Failure to respond to fluid resuscitation: CVP low= continuous bleeding. CVP high= tension pneumothorax -cardiac tamponade- cardiac contusion N.B Of Reactionary Hemorrhage: a. Resuscitation by fluids or blood transfusion. b. Secure legation or angiographic embolisation of the bleeding site. N.B Of secondary hemorrhage : a. Surgical legation of the bleeding vessel proximal to the eroded site. b. Or packing of the bleeding site if tissues are friable from infection which makes legation difficult + broad spectrum antibiotics. 33 General Surgery Metabolic response to injury Definition:  Metabolic disturbances follow all forms of trauma (operations, burns and fractures,…)  Proportionate to the severity of the trauma and to the nutritional state of the patient.  At first (6:8 days): Catabolic.  Followed (10-60 days) by an anabolic phase with repair of tissue, repletion of stores of fat and proteins and weight gain. It is controlled by growth hormone, androgens and ketosteroids. Catabolic Phase: 1. ↓Water excretion: - Increased of ADH from the posterior pituitary. - In the first 24:48 hours urine excretion is reduced to 500 ml per day. 2. ↓Sodium excretion: - Drops from 100 mEq to 10 mEq per day. - Due to Increased secretion of aldosterone. - The duration is 5:6 days. - Independent on whether Na+ is given or not. 3. ↑Potassium: - Increased urinary excretion (maximal the day of operation to 48hours). - It increases from 70:100 mEq to 100:140 mEq. - It is due to mobilization and excretion of intracellular K+. 4. ↑Protein: - Increase the nitrogen excretion from a normal of 10:12 gm daily to 30 gm/day. - Skeletal muscle breakdown  Aminoacids used for gluconeogenesis and proteins. - Through the adrenocortical hormones. (abscent in Addison's disease) 5. ↑Glucose: - Glycogen breakdown  blood glucose level rises - Due to Adrenaline and Glucagon. - Also stimulation of gluconeogenesis from amino-acids due to increased cortisol. - known as diabetis of injury. 6) Fat: - Under control of interleukins and TNF. - Lipases release glycerol and fatty acids. - Glycerol is used for gluconeogenesis and fatty acids are oxidised for energy. 45 General Surgery Anabolic phase - Starts from the second week and may last for several weeks. There is a positive nitrogen balance (3:5 gm nitrogen per day). The patient will gain weight and strength. The responsible factors are the growth hormone and gonadal hormones. later the patient restores body fat previously lost. Objective of Metabolic Response 1. Mobilization of nitrogen and K+  raw materials for the healing of wounds 2. Conservation of Na+ and water  maintain plasma volume after haemorrhage. 3. A well-nourished person shows catabolism vigorously  heals well. While the malnourished dose not  wound dehiscence or non-union of fractures. Practical Applications: 1. First 24:48 hours after operation water is administered excessively, water intoxication results. An overload of 1.5 litres  neausea and disorientation. An overload of 2.5 litres  metal lethargy. If more  convulsions and coma. 2. Excessive administration of saline in the early post-operative period  Na+ retention and secondarily water retention. 3. Administration of K+ in the first 24hours after operation  high level of K in the blood. ----------------------------------------- A system for post-operative fluid administration: 1. In the first 24hours give 2 litres of glucose5%. 2. On the following day give 2litres of glucose 5% and 500ml of saline. 3. From the 4th day add 20mEq of K+ is added to each litre to give a total of 50 mEq/day. 46 General Surgery Blood Transfusion & Blood products Indication for Blood Transfusion: (restore blood volume).  In acute haemorrhage.  During major operation.  Postoperatively after major surgery.  Preoperative blood transfusion is needed if Hb is less than ↓ 8 gm/dl.  To arrest haemorrhage in haemorrhagic states. Blood Sparing Strategies 1. Pre-operative autologous blood donation:  In elective surgery where blood will be lost and where Hb is at least 11-12 gm/dl.  If the blood is not used it will be wasted  If the patient needs more blood the advantage is lost. 2. Erythropoietin:  Used in the anaemia associated with renal failure and in major surgery.  It is given subcutaneously 600 u/kg 3 times weekly and on the day of surgery.  It is usually given with oral or I.V. iron therapy. 3. Acute Normovolemic Haemodilution:  Following induction, 1000 ml of blood are removed and replaced with crystalloids.  The blood is given to the patient when it is needed during or after the surgery.  The patients Hb must be initially high. 4. Intraoperative Blood Salvage:  In clean operations using the cell saver equipment.  Aspirates, anticoagulants and filters the extravasated blood.  Then red cells are washed and given as packed red cells. It is usually used in liver transplantation. 47 General Surgery Blood and blood products I) Stored whole blood:  Collected into a sterile plastic bag.  The bag contains 75 ml of anticoagulant solution CPDA (Citrate Phosphate Dextrose Acid).  Stored at 4°C and can be used within 21 days.ood and blood products  Disadvantage of stored blood 1. Citrate anticoagulant 2. Has an acid pH (6.6-6.8) 3. High level of K+ (from stored red cells) 4. High ammonia (from red cells adenosine) 5. Reduced red cell (2,3-DPG)  impaired release of oxygen from oxy-Hb. 6. White blood cells and platelets are destroyed after 24 hours in the stored blood. 7. Also the levels of clotting factors V and VIII fall quickly. II-Blood fractions 1. Packed Red Cells:  Used in chronic anemia, elderly, cardiac and children and will avoid overload.  The plasma is replaced by 100 ml of a crystalloid solution containing NaCl, adenine, glucose and mannitol (SAG-M blood). 2. Platelet Rich Plasma:  It is prepared by centrifugation of freshly donated blood.  It is used in thrombocytopenia and during surgery. 3. Platelet Concentrate:  Prepared by centrifugation of platelet rich plasma.  They also carry HLA antigens.  reaction (with repeated transfusion).  Indications: Thrombocytopenia, DIC, Massive transfusion, aplastic anaemia. 48 General Surgery 4. Plasma Products: a.Human albumin 4.5%: It is prepared by repeated fractionation of plasma followed by heat treatment. Free from the danger of transmission of hepatitis. Stored for several months in liquid form at 4°C. It is used in burns and in hypoproteinaemia. There is salt-poor human albumin 20% used in cirrhotic patients with ascites. b.Fresh-Frozen Plasma FFP: Plasma removed from fresh blood and rapidly frozen and stored at -40°C. It is a good source of all the coagulation factors, albumin and immunoglobulins. It is used during surgery on liver failure, in Christmas disease and haemophilia. It is not used as plasma expander. c. Cryoprecipitate:  FFP at -4°C, a glutinous precipitate remains.  It is stored at -40°C. Very rich source of factor VIII, Von Willebrand factor and fibrinogen.  Used in treatment of haemophilia, Von Willibrand's disease and is given I.V. d. Factor VIII and factor IX concentrates:  They are now available in freeze-dried form. e. Fibrinogen:  Used in severe depletion of fibrinogen e.g. DIC  Carries a high risk of hepatitis. f. Immunoglubins Ig G:  Provide passive immunity to non-immunised patients exposed to serious infection (viral or bacterial) e.g. human tetanus immunoglogin. 49 General Surgery Changes occur during storage of blood Red cell viability Platelet viability Coagulation factor V & XIII Potassium content (mmol/L) 0 days 95% 95% 95% 3.5 7 days 90% 0% 30% 10 14 days 85% 0% 30% 25 21 days 75% 0% 30% 30 Indications for transfusion Product Whole blood Indication Class III % haemorrhage Precaution Storage life ABO &Rh. 21 days Packed RBC Severe anaemia ABO &Rh. 21 days FFP Bleeding due to non-specified coagulation factor deficiency. coumarin overdose. ABO 1 year at -40 °C Platelet Primary or secondary thrombocytopenia ABO 24-72 hours ABO 1 year at -40 °C Cryoprecipitates Bleeding with fibrinogen depletion VIII & fibrinogen. Factor VIII Factor IX Haemophilia A. Haemophilia B. coumarin overdose. 2 years Albumin Acute volume expansion. Hypoalbuminaeia. 4 years 50 General Surgery Complication of Blood Transfusion I - Transfusion- related complication: 1. Haemolytic reactions. Aetiology:  Antibodies in the recipient's blood against antigens of the donor's cells.  Mostly due to human error. Clinically  Present after the transfusion of less than 50 ml.  Fatal more than 200 cc  Fever, chills, constricting pain in the chest, dyspnoea and pain In the flanks.  tachycardia and hypotension  Anaesthetized patients: haemolytic reactions are sudden tachycardia, hypotension and bleeding tendency.  Major hemolytic reaction will lead to  haemoglobinuria, jaundice and acute renal failure, DIC. Management  Stop transfusion  Send for repeat typing and matching.  Infusion of Lactated Ringer and IV corticosteroids.  Osmotic diuretic as mannitol may be needed.  IV infusion of sodium bicarbonate may be indicated. 2. Pyrogenic reactions.     Commonest complication. Present by: chills, fever, headache, nausea and vomiting. Due to minor bacterial contamination. Transfusion is stopped and the patient is given IV aspirin or paracetamol. 3. Allergic reactions.      Range from mild itching and urticaria to a severe laryngeal oedema. Due to antibodies against a protein in the donors plasma Common with repeated transfusions in the past. Treatment is by antihistaminic and corticosteroids. If the reaction is severe, blood transfusion should be stopoed. 51 General Surgery 4. Post- transfusion purpura:  In patients who have been previously sensitized to a foreign platelet antigen. 5. Immunological sensitization: - Antibodies developed from repeated transfusion. II - Circulatory Overload 6. Congestive cardiac failure.  Occur in elderly persons especially if a large volume administered too rapidly.  It is recommended packed red cells to correct anaemia in elderly persons. III - Transmission of diseases 7. Transmission of infection Viral hepatitis (B or C):  The most feared complication. AIDS / HIV infection can be transmitted by blood or by its products. Syphilis: This is now rare. Malaria: The disease is transmitted only by red cells, not by blood components. Septicemia IV – Others: 8. Hyperkalaemia:  storage of blood  progressive increase of potassium from erythrocytes.  Several units  hyperkalaemia  cardiac arrhythmias or even arrest. 9. Citrate intoxication: - Citrate will bind to the calcium leading to hypocalcaemia - which augments the effects of hyperkalaemia on the myocardium. - If more than 2 units of blood are administered, it is important to administer 10 ml of 10% calcium gluconate for each two units of blood. 10. Hemosidrosis: - Repeated red cell transfusion over many years will cause iron overload of the macrophage system (usually after 100 units) e.g. in thalasaemia. Treatment is by iron chelation therapy with desferrioxamine. 52 General Surgery 11. Air - embolism. Introduction of air through ill-fitting tubing especially if blood is introduced under pressure. Air enters the Rt. ventricle causing an air-lock and Rt. sided heart failure. Treatment: 1. Trendelberg position (air will pass into the veins of the lower limbs) 2. Place the patient on the left side (air will float to the apex of the ventricle) 3. Oxygen therapy. 4. In severe cases aspiration of the right ventricle. 12. Massive blood transfusion:  Definition: - Transfusion of 2500 ml of blood at one time - or 5000 rot or more over 24hours (all body volume).  Effect: 1 hypothermia. - Warm the blood before transfusion - as hypothermia can cause acidosis or cardiac arrest. 2 Hyperkalaemia. (discuss). 3 Citrate intoxication (discuss) 4 Hypocalcaemia. 5 Coagulation failure.: stored blood poor in:  Platelets,  Factor VIII and factor V.  Coagulation factor.  it is recommended to transfuse one unit of fresh frozen plasma and platelets for every unit of stored blood 6 Diminished 02 carrying capacity of red blood corpuscles. 13. DIC: (Discuss) 53 General Surgery Parenteral Fluid Therapy Crystalloid solutions 5% Dextrose: - It contains 278 mmol/l of glucose ( caloric content negligable). - Glucose 5% supplies mainly water. - Pass to IC and EC compartment. Only 7.5% stays in the intravascular compartment. Normal saline (0.9%): - It contains 154 mmol/l Na+, 154 mmol/l Cl-. - 500ml of saline can provide daily requirement of Na+. - GIT losses have to replace by saline volume for volume. Dextrose saline (0.18% saline,4%dextrose): - It contains 30 mmol/l Na+, 30mmol/l Cl- and 222mmol/l dextrose. Ringer`s solution: - It contains 147mmol/l Na+, 4 mmol/l K+ and 2.2 mmol/l Ca++. Hartmann`s solution=Ringer lactate solution: - It contains 131mmol/l Na+, 5 mmol/l K+,29 mmol/l HCO3-, 111mmol/l Cl-, 2mmol/l Ca++. - Ringer lactate solution is the best solution to be used in hypovolaemic shock. Colloid Solutions Albumin 4.5%: - Molecular range from 45000 to 70000. - It stays in the intravascular space. - It corrects hypovolaemia but is expensive. Gelatin (e.g. Haemaccel): - It is produced from hydrolysis of bovine collagen. - Half life in circulation 8:10 hours. - Contains K and Ca++. So if mixed with citrated blood in a giving set coagulation of blood 54 - Chapter 4: Acute Haemorrhage and Blood Transfusion o Neoplastic, e.g., haematuria in renal cancer. • Bleeding diathesis can increase the amount of traumatic and pathological bleeding, or cause bleeding with little or no trauma (spontaneous haemorrhage). Pathophysiological response to haemorrhage The pathophysiological response to haemorrhage has two aims 1. Stopping the bleeding • Vasoconstriction and retraction of the intima of the injured vessel. • Platelet plug. • Blood clotting. , -- Capillary · Pressure Capillary refill +-+ heart rate Arteriolar constriction Constriction -venous +-+ contractillty +-+ TPR I++ Aldosterone Venous Arteriolar constriction ++ Na reabsorption ++ Blood volume capacitance ++ Arterial Prossuro towards normal ++ Arterial Pressure towards normal Fig. 4.1. Main compensatory mechanisms for haemorrhage. 2. Maintaining effective circulatory volume and perfusion of critical tissues (brain and heart), at the expense of less critical tissues (skin, skeletal muscle and splanchnic area). This is achieved by neural and endocrine factors (Fig. 4.1 ). A. Neural factors. A sympathoadrenal discharge develops due to decrease in stimulation of arterial baroreceptors (aortic arch and carotid sinus) and atrial stretch receptors leading to reduction of the normal inhibitory discharge in the vagus and glossopharyngeal nerves on the vasomotor centre with consequent stimulation of the sympathetic system. The effects include • Constriction of veins, which normally contain two-thirds of the blood volume, displaces blood from the capacitance side of the circulation into the heart. • Constriction of arterioles raises the peripheral resistance but this is not uniform. It involves mainly the arterioles of the skin, skeletal muscle, and splanchnic area. Perfusion of the heart and brain is maintained because heir metabolic needs override the alpha-adrenergic vasoconstrictor discharge. • Increased rate and strength of cardiac contraction. Chapter 4: Acute Haemorrhage and Blood Transfusion 1111111111 B. Endocrine factors • Catecholamine discharge occurs from the adrenal medulla and from the nerve endings throughout the autonomic nervous system. They increase the heart rate and myocardial contraction and cause constriction of the arterioles of the skin, kidney and viscera. ones hormone and glucagon are As cortisol, stress growth • The metabolic hormones ACTH, increased. Insulin release is inhibited by adrenaline and noradrenaline. • The renin-angiotensin aldosterone system. The juxtaglomerular cells of the afferent renal arterioles secrete renin in response to renal hypoperfusion. Renin splits angiotensinogen to angiotensin I, which is converted to angiotensin II by a converting enzyme in the lung. Angiotensin II is a powerful vasoconstrictor and stimulates sodium and water retention by a direct action on the kidney as well as indirectly through release of aldosterone from the zona glomerulosa of the Intravasal adrenal cortex. Angiotensin-mediated vasoconstriction takes some 20 minutes to occur, whereas baroreceptor-vasoconstriction occurs within seconds. Tintin now ADH (vasopressin). Blood loss greater than 10% stimulates ADH release. ADH increases the permeatJility of the renal collecting tubules allowing water absorption into the hypertonic renal medu~ary interstitium. With severe haemorrhage high levels of ADH also cause vasoconstriction. C. Transcapiilary refill. Reduction of blood volume and constriction of arterioles causes a fall in capillary hydrostatic pressure and promotes movement of fluid from the interstitium into the capillaries, resulting in increased blood volume. • If ovulatory compensationphase a spasmof changes celldistressphase Capillaryrefill Clinical picture of haemorrhage decompensation irreversible failure The manifestations depend upon the amount of blood loss. Its rate and on cardiovascular reserve. Thus, loss of only 500 ml of blood may cause hypotension in a patient with coronary artery disease, whereas in a healthy young adult, losses greater than 1500 ml may not lower systolic pressure initially. The following are the clinical manifestations of hypovolaemia. Symptoms • Weakness and fainting especially when standing. • The patient feels cold and thirsty. Signs • The patient looks tired. With decreasing cerebral perfusion, the mental status may vary from anxious to drowsy but the patient usually remains al.ert. • Pulse and blood pressure. With mild blood loss (less than 500 ml), pulse and blood pressure may remain normal thanks to the efficient compensatory mechanisms. With more blood loss, tachycardia develops but the blood pressure remains stable. With further blood loss, however, the compensatory mechanisms can no longer maintain the blood pressure and progressive hypotension develops (Table 4.1 ). • Pulse pressure (PP) decreases leading to a thready pulse. • Respiratory rate. Tachypn~a and air hunger. • Hypothermia, which predisposes to coagulopathy and should be avoided. IIIIIIII Chapter 4: Acute Haemorrhage and Blood Transfusion • Skin becomes pale, cold and sweaty with slow capillary refill and collapsed veins. • Oliguria results due to diminished renal perfusion. Table 4.1. Clinical parameters in different classes of haemorrhage. - - -- -- - - - -C -la_s_s_l Blood loss (in 70 Kg person) 15- 30% (7501500 ml) (1500-2000 ml) Normal to anxious Anxious to restless Aggressive to drowsy Drowsy to unconscious Skin Normal Pale and cold Pale and colder Pale and very cold Capillary refill Normal >2 sec. >2 sec >2 sec undetectable Pulse/minute <100 100-120 100-140 >140 - Systolic Normal Normal (supine) Low Low - Diastolic Normal Raised Low Low - Pulse pressure Normal Low Low Low 14 -20 20-30 30- 35 >35 >30 20-30 10-20 0-10 Mental status Up to 15% (750 ml) 30-40% >40% (2000 ml) Blood pressure Respiratory rate Urine (ml/h) Estimating blood loss Blood volume is estimated as 70 ml/Kg in adults and 80 ml/Kg in children. In any patient with haemorrhage, it is of importance to have a rough estimate of the amount of blood loss determined from the following. • Clinical data. Four classes of haemorrhage are recognized based on clinical changes in haemodynamic parameters and indices of tissue perfusion (Table 4.1 ). This table provides only general guidance. • Type of injury. The haematoma around a closed fracture of the tibia may contain 5001500 ml of blood, that around a fractured shaft of femur, 500-2000 ml; that in a fractured pelvis, 2000-3000 ml. • Blood loss at operation is the sum of the amount in the suction reservoir and the amount mopped up by the swabs, the latter is calculated as the difference in swab weight after and before operation multiplied by a correction factor of 1.5-2 depending on the magnitude of the operation. Investigations • Complete blood picture, including haematocrit. The initial haematocrit value is often normal (RBCs and plasma are lost in the same ratio). Some 4-6 hours later, serial haematocrits will show a reduction. Haemodilution is caused by movement of interstitial fluid into the circulation and because of crystalloid replacement of lost blood. • Coagulation profile. • Cross matching. Treatment of haemorrhage 1. Stop haemorrhage. First-aid treatment is by packing, pressure, and position. A skin wound is covered by a dressing, and pressure is applied manually, by a 1.5 b4 5 Crystalloid Chapter 4: Acute Haemorrhage and Blood Transfusion - sphygmomanometer cuff or by a bandage. Tourniquets are contraindicated because of complications unless the limb is going to be amputated. Elevation of the limb above the heart level stops venous and decreases arterial bleeding. Other examples of first aid treatment include the pneumatic anti-shock garment (PASG), which can tamponade lower limb, pelvic and abdominal haemorrhage. The garment increases peripheral resistance and so raises the blood pressure. Another example is balloon tamponade of haemorrhage from oesophageal varices. The definitive management depends upon the cause of bleeding. 2. Restore blood volume. A large bore cannula is inserted in a large peripheral vein, preferably in the upper limb, or by a cut down on the long saphenous vein, if necessary. Volume replacement depends on the class of the haemorrhage. Class II • The deficit is estimated at 15-30% (750-1500 ml/70 kg). • The replacement solution is lactated Ringer's. • The amount is 3 times the estimated deficit (-3 L). The 3: 1 rule serves to replenish the interstitial fluid volume when the crystalloid diffuses out of the capillaries. • Administration. Two litres are given as a bolus and the response is monitored. If there is definite improvement: the remaining litre is given more slowly followed by the maintenance requirements and continued observations (a haematocrit <30 requires blood transfusion). If there is moderate improvement, the possibilities are inadequate replacement, continuing haemorrhage or myocardial insufficiency. Cardiac tamponade and tension pneumothorax must be excluded. Blood transfusion is started if bleeding is still active. Cardiac Class Ill and IV means Aorns Aneurysm failure • The management is as for class II but these patients need blood transfusion. The initial volume of transfused blood is that of the estimated deficit (1500-2000 ml). • Failure to improve and a rising CVP indicate tension pneumothorax, cardiac tamponade, or cardiac failure. If these are excluded and the patient does not improve, major thoracic, abdominal, or pelvic injury is usually present and calls for immediate operation to control the bleeding. Clean blood in the thorax or abdomen can be aspirated, anticoagulated and then transfused back into the patient (autotransfusion), if a cell-saver is available. • Transfusion should continue until the haematocrit has reached 30%, the urine output 50 ml/hour, and the CVP has risen to the upper half of the normal range. 3. Optimize oxygen delivery. Forty percent oxygen is given for class II haemorrhage and 100% for classes Ill and IV. Intubation and mechanical ventilation and the use of inotropes (dopamine and dobutamine), vasodilators and vasopressors may be 40 necessary if raising oxygen carrying capacity by blood transfusion does not improve lass oxygen delivery. 01 31 4. Monitoring is important to prevent the clinical sequelae and complications of hypovolaemic shock, i.e., cardiac arrest, adult respiratory distress syndrome (ARDS), acute renal failure, GIT dysfunction with stress bleeding, and disseminated intravascular coagulation (DIC). 2 What to monitor? • The parameters in Table 4.1 suffice if the patient is fit and responds quickly to bolus infusion of 2 litres of Ringers lactate solution. A Foley catheter is necessary to morphine is fine body core temperature 25 normally Any increase 111111!1 Chapter 4: Acute Haemorrhage and Blood Transfusion Perfusion means 055m monitor urine output. Serial rectal temperatures, haematocrits and cardiac monitoring (ECG for early detection of shock-induced arrhythmias) are important. • preload Invasive monitoring is needed if the patient is old or has compromised cardiac reserve , class Ill or IV haemorrhage, or does not respond well to initial crystalloid administration. Central venous pressure (CVP), blood gases, and blood lactate (index of anaerobic metabolism), are necessary. A pulmonary artery catheter is required in complex situations to monitor the function of the left side of the heart. RIFailure to respond to treatment is due to either • Continuous bleeding. • Pump failure (tension pneumothorax, cardiac tamponade, or cardiac contusion). Pump failure is distinguished by a high CVP reading. • Irreversible shock catheter Swansans Blood transfusion Blood is a precious commodity. Its only source is the human being, who willingly parts with some of his life fluid to save the life of a fellow human. Handling of blood should, therefore, be conducted with the deserved dignity, and it should also be administered in its proper indication. Advances in technology allowed the evolution of synthetic blood substitutes that have the ability to carry oxygen. Though still not the perfect substitute, with further refinement these substances are expected, in the future, to solve the problem of limited sources and complications of blood transfusion. Collection and storage of blood For standard transfusion blood is collected into a citrate anticoagulant solution which also contains dextrose to preserve the viability of RBC's during storage. One blood bag (unit) contains 70-100 ml of the anticoagulant and 400-450 ml of blood. Blood must be kept at 2-6°C during storage. Common blood products • Packed red cells (red cell concentrate). The transfusion of packed red cells is very useful in anaemic patients, in the elderly and in cardiac patients as it improves the oxygenation ability without overloading the circulation. • Fresh frozen plasma. Plasma removed from fresh blood is rapidly frozen and stored at -40°C. It is a good source of all the coagulation factors. It is useful to correct coagulation disorders in haemophilia, Christmas disease and in liver failure. • Platelet concentrates. The amount obtained from one unit of blood will increase the circulating number of platelets by 10,000 to 15,000/ul. As the half life of platelets is short, they should be freshly prepared. They are very useful in patients with thrombocytopenia. • Cryoprecipitate. This is prepared from fresh frozen plasma and is very rich in factor VIII and fibrinogen. It is stored at -40°C. Chapter 4: Acute Haemorrhage and Blood Transfusion - Possible complications of blood transfusion • Immunological complications a. Incompatible red cells b. Incompatible white cells Acute haemolytic reaction c. Incompatible platelets Pyrogenic reaction Purpura d. Reaction to a protein in the plasma - Allergic reaction (a) Acute haemolytic reaction. Most often these reactions are due to the presence of antibodies in the recipient's blood against one or more of the antigens of the donor's red cells. Clinically haemolytic reactions present after the transfusion of less than 50 ml by fever, chills, constricting pain in the chest, dyspnoea and pain in the flanks. Examination reveals tachycardia and hypotension. In anaesthetized patients, the only manifestations of haemolytic reactions are sudden tachycardia, hypotension and bleeding tendency. A major haemolytic reaction will lead to haemoglobinuria, jaundice and acute renal failure due to acute tubular necrosis. Consumption coagulopathy will lead to generalized bleeding tendency. Management o Stop the transfusion immediately. o Send the donor's blood and a sample of the patient's blood for repeat typing and matching. o Correct shock by infusion of crystalloid solution (Lactated Ringer) and IV corticosteroids. o Insert a Foley catheter and check that there is an adequate urine output. An osmotic diuretic as mannitol may be needed. Keep an alkaline urine to protect against acute renal failure. IV infusion of sodium bicarbonate may be indicated. o Should the patient develop acute renal failure, he must receive the appropriate treatment. (b) Pyrogenic reactions. These are the commonest unpleasant consequences of blood transfusion. The patient develops chills, fever, headache, nausea and vomiting. These reactions are due to the presence of recipient antibodies against some components of the donor's white blood cells. Transfusion is stopped and the patient is given IV aspirin or paracetamol. (c) Post-transfusion purpura may develop in patients who have been previously sensitized to a foreign platelet antigen. (d) Allergic reactions may develop due to immunoglobulin antibody in the recipient complexing with a protein present the donor's plasma. These range from mild itching and urticaria to a severe reaction with laryngeal edema and collapse. These reactions are common in those patients who received many transfusions in the past. Treatment is by antihistaminics and corticosteroids. If the reaction is severe, blood transfusion should be stopped. • Congestive cardiac failure. This is liable to occur in elderly persons especially if a large volume of blood is administered too rapidly. It is recommended to transfuse packed red cells rather than whole blood to correct anaemia in elderly persons. ..rl)I • Chapter 4: Acute Haemorrhage and Blood Transfusion Transmission of infection o Viral hepatitis (B or C). This is now the most feared complication. The virus can be transmitted by whole blood or blood products. It is obligatory to test donors for hepatitis viruses. o AIDS/HIV infection can be transmitted by blood or by its products. o Syphilis. This is now rare. Spirochetes cannot survive at the blood bank temperature for more than 4 days. o Malaria. The disease is transmitted only by red cells, not by blood components. o Septicemia. Bacteria can survive, but they cannot multiply significantly in refrigerated blood. However, if the blood is allowed to warm, bacteria can grow and Gram-negative endotoxins can cause septic shock. • Hyperkalaemia. With prolonged storage of blood, there is progressive loss of potassium from erythrocytes into the plasma. Transfusion of several units of aged blood may produce cardiac arrhythmias or even arrest due to hyperkalaemia. • Citrate intoxication: Excess citrate will bind to the recipient's calcium leading to hypocalcaemia which augments the effects of hyperkalaemia on the myocardium. If more than 2 units of blood are administered, it is important to administer 10 ml of 10% calcium gluconate for each two units of blood. • Air embolism. • Transfusion related acute lung injury (TRALI). This is the result of incompatibility between donor's antibodies and recipient granulocytes. It gives a clinical picture similar to ARDS. • Complications of massive blood transfusion. This implies transfusion of 2500 ml of blood at one time or 5000 ml or more over 24 hours. o Hypothermia. A special warming unit should be used to warm blood before transfusion as hypothermia can cause acidosis and cardiac arrest. o Hyperkalaemia. o Hypocalcaemia. o Coagulation failure. This is due to the dilution of clotting factors and platelets when large volumes of stored blood are being used to replace blood losses, because stored blood is poor in platelets, factor VIII and factor V. In these situations, it is recommended to transfuse one unit of fresh frozen plasma and platelets for every unit of stored blood. o Diminished 02 carrying capacity of red blood corpuscles. Alternatives to homologous blood transfusion 1. Autologous blood transfusion: A patient who is going to have a major elective operation can donate some units of his own blood over several days. The blood is kept in the refrigerator to be given back to him during surgery. 2. Preservation of the blood lost during surgery and its reinfusion to the patient. This needs a special apparatus (cell saver). Chapter 4: Acute Haemorrhage and Blood Transfusion Table 4.2. Indications for transfusion of blood and its products Product Indication Precautions Storage life Whole blood Class Ill & IV haemorrhage ABC & Rh 21 days Red cell concentrates Severe anaemia ABC & Rh 21 days Fresh frozen plasma Bleeding due to non-specified coagulation factor deficiency ABO 1 year at - 40°C Coumarin overdose Platelet concentrates Primary or secondary thrombocytopenia ABO 24 - 72 hours Cryoprecipitates of factor VIII &fibrinogen Bleeding with fibrinogen depletion ABO 1 year at - 40°C Factor VIII Haemophilia A Factor IX Haemophilia B. Coumarin overdose Albumin 5% or 20% Acute volume expansion. Hypoalbuminaemia 2 years 4 years Chapter 5: Haemostasis - CHAPTER 5 HAEMOSTASIS Introduction: Haemostasis is the physiological arrest of bleeding. It involves vasoconstriction, platelet plug formation and fibrin deposition to form a stable clot sealing the disruption in the vessel wall. A fourth mechanism, fibrinolysis breaks down the clot, restoring vascular patency after bleeding has stopped. Natural haemostasis sometimes fails leading to excessive bleeding or thrombosis. Natural haemostasis Primary haemostasis Arrest of haemorrhage within the first few minutes is achieved by: CHAPTER CONTENTS • Introduction • Natural haemostasis o Primary haemostasis o Secondary haemostasis o Fibrinolysis • Heemostatic disorders o Congenital disorders o Acquired disorders • Preoperative evaluation of haemostasis • Excessive operative and postoperative bleeding • Surgical haemostasis 1. Vasoconstriction of the disrupted vessels. This is achieved by: • Contractile proteins in the endothelium (even capillaries constrict). • Neurogenic reflexes. • Direct smooth muscle stimulation (spasm). • Vasoconstrictors , e.g. thromboxane. Vasoconstriction is more efficient in arteries than veins because arteries contain more muscular fibres. Vasoconstriction is less effective in the following conditions: o When a vessel is partially injured. o In stiff atherosclerotic vessels. o In large veins (poor muscle coat). 2. Platelet plug. Platelets serve the following haemostatic functions: • Adhere to exposed subendothelial collagen. • Release the contents of their granules, e.g. ADP, and serotonin. • Aggregate to form a plug that seals the bleeding vessel. Thromboxane from platelet membrane phospholipid, ADP, serotonin, thrombin etc, are responsible for aggregation. • Platelet phospholipid has a vital role in blood coagulation. 3. Tamponade of the bleeding by surrounding tissue tension. Interstitial haemorrhage tends to be less profuse than external or internal haemorrhage. Secondary haemostasis: Maintenance of haemostasis after the first few minutes requires that the platelet plug be reinforced by fibrin deposition, i.e. coagulation otherwise, the soft platelet plug may be washed away be the blood flow. Coagulation is activated by two mechanisms. - Chapter 5: Haemostasis 1. Extrinsic; initiated by activation of factor VII upon admixture of plasma and tissue factor. 2. Intrinsic, initiated by activation of factor XII upon contact with a non-endothelial surface, more directly by activation of factor IX through activated factor VII. Intrinsic pathway Extrinsic pathway '"""doilier collage, vu tissue factor I Vila OCI1 - - - - Xlla ! XI - -- - Vlll l X PL Xa ~1 PL Prothrombin Thrombin (Ila) Fibrinogen Fibrin monomer XIII stable fibrilpolymer I hos holi id . The common pathway is activated when activation of the intrinsic and extrinsic pathways leads to activation of factor x, and eventually to the formation of the fibrin clot (Fig. 5.1 ). Sequential activation occurs locally; any activated coagulation factor spilling into the general circulation is neutralized by inhibitors such as antithrombin Ill and proteins C and S. Deficiency of these proteins may cause spontaneous thrombosis, e.g. mesenteric vascular occlusion . Fibrinolysis plasminogen ...0 i > ;:; u Ill QI ::, fibrinogen rn rn i= plasmin- FOP Once haemostasis is achieved, the clot obstructing the FiQ. 5.2. Fibrinolysis vessel is no longer needed. Circulating plasminogen and tissue plasminogen activator bind to the fibrin clot leading to local formation of plasmin which digests the clot and restores vascular patency (Fig. 5.2). Circulating inhibitors neutralize plasminogen activators and plasmin which form or overflow into the circulation. The products of fibrin digestion by plasmin are called fibrin degradation products (FOP). D- Chapter 5: Haemostasis - dimers result from plasmin cleavage of cross linked fibrin and constitute a marker of fibrinolysis. Hypercoaguable states Haemostasis disorders:~ Bleeding diathesis Hypercoaguable States: An acquired tendency to thrombosis occurs in pregnancy, estrogen use (HRT or contraception), and malignancy. This tendency is increased if there is an associated inherited thrombohilia, e.g. deficiency of a natural anticoagulant (antithrombin Ill, protein C or protein S). Haematology consultation is required for a personnel or family history of spontaneous/recurrent thrombosis whether arterial and/or venous as well as obstetric history of recurrent miscarriages. Surgical patients should have standard DVT prophylaxis. Estrogen should be stopped 1 month before elective surgery. Bleeding diathesis: Congenital or acquired Congenital disorders E 1. Haemophilia A and B: These are due to deficiency of factors VIII and IX respectively. Inheritance (in both) is sex-linked (from females to males). Manifestations vary from frequent episodes of spontaneous bleeding starting in childhood, (<1% of factor activity). to bleeding only after trauma or surgery (factor level 5-20% of normal). Patients are liable to recurrent haemarthrosis. Management involves: Infusion of factor concentrate within 1 hour before surgery and for 10 days thereafter. Avoiding aspirin and the nonsteroidal anti-inflammatory drugs (NSAIDs) because of their anti-platelets effect, and avoiding IM injections (large haematomas can develop). As the patient will need repeated transfusion.he needs vaccination against hepatitis 8. 2. von Willebrand disease (vWD): von Willebrand disease, together with haemophilia A and 8, constitute more than 95% of inherited coagulopathies. Inheritance is autosomal dominant with variable expression. vWD is due to deficiency of vW factor which enhances platelet adhesion and acts as a carrier to factor VIII, preventing its premature destruction. Manifestations are due to platelet and coagulation problems. Treatment is to supply vWF and cryoprecipitate. Acquired disorders These are more prevalent than congenital ones. E 1. Hepatic disorders: Both acute and chronic liver diseases may be accompanied by haemostatic abnormalities. Aetiology is multifactorial. - Chapter 5: Haemostasis • Coagulation factors: o Decreased concentration of all clotting factors except factor VIII and vWF (from endothelium). o Dysfibrinogenaemia. Defective polymerization of the fibrin clot. o Antithrombin level is decreased, this contributes to intravascular coagulation in cirrhotics. Prothrombin time (PT) is the first to be prolonged (decreased synthesis of factor VII) which has a short half life. In more severe diseases, partial thromboplastin time (PTT) is also prolonged (decrease synthesis of other factors, e.g. V, IX and X). • Platelets: o Thrombocytopenia due to splenic sequestration or destruction due to hypersplenism. Gtibody o Abnormal function due to preponderance of small, less active platelets. The bleeding time is, however, normal in most cirrhotics. • Fibrinolysis: 9 Stop plasminogg o Reduced synthesis of inhibitors of fibrinolysis, e.g., alpha 2 anti-prothrombin. o Impaired clearance of plasminogen activators. Fibrin degradation products (FOP) level may increase. Like DIC • Treatment: o Vitamin K administration. bit plated o In the setting of bleeding or an invasive procedure give: are fire • Fresh frozen plasma (FFP) if PT or aPTTT >1.5 times normal. • Cryoprecipitate to correct severe hypofibrinogenemia (<100 mg/di). o Desmopressin (0.3 ug/kg) can raise the levels of factor VIII and vWF, and shorten the bleeding time before an invasive procedure. 2. Vitamin K deficiency: The sources of this fat soluble vitamin are the diet and bacterial synthesis in the colon. Bile is necessary for its absorption. Causes of deficiency include: • Inadequate diet (or TPN). • In debilitated patients given prolonged broad spectrum antibiotics (reduce colonic bacteria). • Cholestatic jaundice. • Malabsorption. • Oral anticoagulants. Vitamin K is a co-factor in the synthesis of factor II, VII, IX, and X. Deficiency leads to easy bruising and increased traumatic bleeding. Both the PT and PTT are prolonged. Treatment is with vitamin K1 by slow IV infusion (5-10 mg), or daily IM injections for 3 days (10-20 mg/day). In an emergency, factor concentrates, (II, VII, IX and X), or fresh frozen plasma may be needed as well as blood. Chapter S: Haemostasis - 3. Disseminated intravascular coagulation (DIC): Two processes occur. • Widespread activation of coagulation within the circulation leading to consumption of coagulation factors, including fibrinogen, and to depletion of platelets. This is due to entery of procoagulant substances into the circulation. • Stimulation of fibrinolysis by increased levels of fibrin degradation products (FOP), worsen the coagulopathy by inhibiting fibrin polymerization. Causes include: • Septicaemia. • Severe shock, trauma, and burns. • ABO incompatible transfusion. • Malignancies, e.g., metastatic carcinoma of the lung, pancreas, stomach, prostate, and leukaemia. • Obstetric accidents (eclampsia, abruptio placenta, amniotic fluid embolism, and retained dead fetus). Diagnosis is suspected by: • Diffuse bleeding from wounds, incisions, drain and venopuncture sites. • Widespread bruising, purpura and mucosa! bleedtng. • Occasionally, the thrombi are not lysed quibkly and ischaemic manifestations occur, e.g., gangrene of skin and digits. • Uncoagulable blood in severe cases. Laboratory features include: • Thrombocytopenia. Prolongation of PT, PTT and low fibrinogen level (N=2-4 g/L). • Raised level of FOP and O-dimers. Treatment: • Treatment of the underlying cause to stop the cycles of coagulation/fibrinolysis, e.g. draining an abscess and antibiotics for infection. • Replacement of consumed coagulation factors and platelets with fresh frozen plasma (3-4 units initially) and cryoprecipitate when available (it is rich in factor VIII and fibrinogen), and platelet transfusion (10-12 packs may be needed initially). • Blood transfusion to restore circulating blood volume and oxygen carrying capacity since hypoxia exacerbates DIC. • Heparin is only used is 'there is a large vessel thrombosis. 4. Anticoagulants: Anticoagulants are used to prevent or treat arterial or venous thromboembolism. Bleeding may occur if the dose is not properly adjusted. IIIIIIIIII Chapter 5: Haemostasis A problem arises when a patient on warfarin requires surgery. Preoperatively the_ INR must be allowed to drop below 1.5 before the surgery to avoid excessive bleeding. This is achieved by stopping the daily warfarin dose for 4-5 days before elective surgery or using FFP in an emergency (or recombinant factor VIia to avoid risk of blood component therapy. An INR <1.5 must be confirmed before surgery. Preoperative low molecular weight heparin is required if stopping warfarin is associated with a high risk of recurrent thrombosis. LMWH, e.g. enoxaparin, 1 mg/Kg SC every 12 hours is started 36 hours after the last dose of warfarin and stopped 24 hours before operation. Postoperatively LMWH is restarted 24 hours post-procedure. Warfarin is restarted on postoperative day 1 at the preoperative dose. Stop heparin and continue with warfarin when the INR reaches target level, e.g. 2-3. 5. Massive blood transfusion (Chapter 4) 6. Platelets disorders: Thrombocytopenia: Decreased production by the bone marrow (leukemia, cancer infiltration, viral infection and chemotherapy. Increased destruction (ITP, drug-induced e.g. heparin, thiazides and sulpha). Increased sequestration in hypersplenism. Disorders of platelets' functions: Drugs as aspirin, clopidogrel and NSAIDs inhibit cycloxygenase and prostaglandin synthesis, thus they interfere with platelet adhesiveness. Dipyridamole (Persantin) reduces platelet adhesiveness. • Uraemia and hypothermia can cause platelet dysfunction. N.B.: Aspirin and NSAID should be stopped 7 days before surgery. Preoperative evaluation of haemostasis: All patients scheduled for elective surgery should be evaluated for a possible haemostatic defect by history, examination and, when appropriate, laboratory tests. History: This is the most important part of the haemostatic evaluation. Points to be covered include: 1. Family history of bleeding. If positive in maternal grandfathers, maternal uncles, or a brother.it suggests haemophilias (A or B); in a parent or sibling of either sex, it suggests vWD (autosomal dominant inheritance with variable expression). 2. History of bleeding tendency, e.g., spontaneous bleeding, prolonged bleeding after a haemostatic challenge (circumcision, dental extraction, surgery or trauma), bleeding from multiple sites, or easy bruisability. Chapter 5: Haemostasis IDIII 3. Age at onset of bleeding. A long history and onset in childhood suggest a hereditary disorder. Recent onset in an adult suggests an acquired disorder. 4. Inquire about liver disease, chronic renal failure, massive blood transfusion and drug intake. 5. Characters of the bleeding: • Defects of primary haemostasis (platelet/vessel abnormalities). Bleeding is ·superficial i.e. skin and mucous membranes, such as petichiae, purpura, easy bruisability, epistaxis, and menorrhagia. Excessive oozing occurs immediately following surgery or trauma and is usually controlled by local pressure. Visceral bleeding, e.g., CNS is not common. • Defects of secondary haemostasis (coagulation/fibrinolysis). Bleeding is deep, e.g. haemoarthrosis, haematomas in muscles, retroperitoneal or visceral, in addition to easy bruisability. Onset following surgery or trauma is delayed and local pressure is usually ineffective. Mucous membrane bleeding is not common. • Excessive fibrinolysis or thrombolytic agents cause generalized bleeding, e.g. from the wound, drain site, or IV sites. Examination: The following points are checked in the preoperative patient if a bleeding tendency is suspected. 1. Cutaneous signs of liver disease, e.g. jaundice, and spider naevi. 2. Skin and mucous membranes are examined for bleeding, petichiae, or bruising. 3. Musculoskeletal system. Muscle haematomas, and haemoarthrosis (coagulopathy). 4. Abdomen. Hepatomegaly, and splenomegaly. The latter may be the cause of platelet sequestration and thrombocytopenia. Tests of Haemostasis Indications: 1. Patients with a personal history or a family history of abnormal bleeding. 2. Patients with diseases or who receive medications that can interfere with haemostasis. Tests of primary haemostasis: 1. Platelet count. Normal=150.000-400.000/ul. • Spontaneous bleeding occurs with counts 10.000-20.000luL. • Prolonged bleeding with minor trauma occurs with counts 20.000-50.000/ul. • Prolonged bleeding with major surgery/trauma occurs with counts 50.000100.000/ul. • No haemostatic abnormality occurs in counts more than 100.000/ul. 2. Bone marrow aspiration and biopsy. • Megakaryocytes are normal or increased in thrombocytopenia due to peripheral destruction or sequestration. Chapter 5: Haemostasis Megakaryocytes are rare in bone marrow damage, e.g., chemotherapy, or replacement, e.g. leukaemias. 3. Bleeding time (BT) is prolonged with platelet and vascular defects. 4. Tests of platelet function (adhesion, release, aggregation) may be necessary when the BT is prolonged but platelet counts are normal. Tests of secondary haemostasis: 1. Prothrombin time (PT) measures the time of cloning through the extrinsic and common pathways which involve factor VII and factors X, V, II and fibrinogen respectively. 2. PartiaJ thromboplastin time (PTT) measures the time of clotting through the intrinsic pathway (factors XII, XI, IX, and VIII) and the common pathway. 3. Thrombin time (Tl) measures the time of clotting after thrombin is added to plasma. It is sensitive to abnormalities of fibrin formation, e.g. due to FOP in DIC. Other tests: 1. Fibrinogen level is decreased in DIC. 2. Fibrin degradation product (FOP) and D-dimer screens for fibrinolysis. 3. Individual coagulation factor assays. 4. Clot stability test evaluates factor XIII, deficiency of which is not detected by the PT or PTT. Excessive operative and postoperative bleeding Causes: 1. Inadequate surgical haemostasis is the commonest cause. If the bleeding persists, it becomes complicated by DIC and the coagulopathy of massive blood transfusion. 2. Haemorrhagic diathesis not detected preoperatively. The PT, PTT and TT are not very sensitive and may be normal even when the deficient factor concentration is down to 20% of normal level. A PT of 2-3 seconds above normal level is