MLS 323 Acquired Coagulation Disorders PDF

MLS 323 1 Acquired coagulation disorders 2 objectives 1 2 3 Describe the hereditary Describe the acquired Interpret the results of coagulation disorders coagulation disorders. first-line tests...

MLS 323 1 Acquired coagulation disorders 2 objectives 1 2 3 Describe the hereditary Describe the acquired Interpret the results of coagulation disorders coagulation disorders. first-line tests used in e.g. factor VIII deficiency investigating acute (Hemophilia A), factor IX hemostatic failure deficiency (Hemophilia B), vWF deficiency.  Disseminated Intravascular Coagulation 3 (DIC)  4  Is considered an “acquired bleeding disorder”  Is not a disease entity but an event that can accompany various disease processes  Is an alteration in the blood clotting mechanism: abnormal acceleration of the coagulation cascade, resulting in thrombosis  As a result of the depletion of clotting factors, hemorrhage occurs simultaneously  Is a Paradoxical Clinical Presentation “clotting and hemorrhage’’.  Pathophysiology  In DIC, tissue factor (TF) release into the circulation from damaged tissues present on tumor cells or from up - regulation of TF on circulating monocytes or endothelial cells in response to pro - inflammatory cytokines (e.g. interleukin - 1, tumor necrosis factor, endotoxin).  The systemic activation of the coagulation system simultaneously leads to thrombus formation and exhaustion of platelets and coagulation factors (results in hemorrhage). This is a disruption of body homeostasis. 5 Clinical conditions associated with DIC 6  7 Clinical feature  Onset maybe Acute or Chronic Acute DIC Develops rapidly over a period of hours Presents with sudden bleeding from multiple sites Treated as a medical emergency Chronic DIC Develops over a period of months Maybe subclinical Eventually evolves into an acute DIC pattern  Signs and Symptoms Most common sign of DIC is bleeding: ❖ Manifested by ecchymosis, petechiae and purpura ❖ Bleeding from multiple sites either oozing or frank bleeding ❖ Cool and or mottled extremities may be noted ❖ Dyspnea and chest pain if pleura and pericardium involvement ❖ Hematuria 8  9 Lab findings: Test Abnormality Platelet count Decreased Factor assay Decreased Prothrombin time (PT) Prolonged Activated PTT Prolonged Thrombin time Prolonged Fibrinogen Decreased Fibrin degradation product (FDP) Increased (+ ve) D-dimer Increased Antithrombin Decreased Schistocytes, thrombocytopenia on peripheral blood smear  10 Vitamin K  Vitamin K is a fat-soluble vitamin essential for the post-translational modification of factors II, VII, IX and X and proteins C and S.  Plants produce vitamin K1, whereas vitamin K2 is synthesized by micro- organisms.  Vitamin K is absorbed in the proximal small intestine in the presence of bile.  The liver stores vitamin K, however only a small amount is stored and without intake deficiency can ensue in a few days 11 Hemorrhagic disease of the newborn  Deficiency may present in the newborn (hemorrhagic disease of the newborn) or in later life.  There is a relatively poor exchange of vitamin K across the placenta.  The neonatal liver stores predominantly K1, which has a more rapid turnover, compared with K2, which is the dominant storage vitamin K in the adult liver.  The newborn also lacks the gut flora to produce vitamin K.  12 Hemorrhagic disease of the newborn  HDN may present with intracranial haemorrhage, gastrointestinal bleeding and bleeding from other sites.  Forms of HDN:. 1. Early HDN. This occurs following maternal ingestion of compounds that can interfere with vitamin K metabolism which may be prevented by the maternal administration of vitamin K before delivery. 2. Classic HDN. Appear when prophylactic vitamin K is not administered, it may appear at any time in the first month of life. 3. Late HDN. This form occurs at 2–12 weeks. It manifests in breast-fed infants who did not receive vitamin K at birth. Other conditions associated with late HDN include cystic fibrosis, alpha 1- antitrypsin deficiency and coeliac disease.  13 Vitamin K deficiency  Adults require a minimum daily intake of vitamin K of 0.1– 0.5 µg/kg.  The absorption of this fat-soluble vitamin is dependent on the presence of bile salts in the upper small intestine.  Deficiency of vitamin K is caused by an inadequate diet, malabsorption or inhibition of vitamin K by drugs such as warfarin.  Broad-spectrum antibiotics may produce a vitamin K-deficient state in those receiving them.  Certain clotting factors/proteins require calcium to bind for activation  Calcium can only bind after gamma carboxylation of specific glutamic acid residues in these proteins  The reduced form of vitamin K2 (vitamin KH2) acts as a cofactor for this carboxylation reaction.  These proteins are known as “Vitamin K dependent” proteins The action of vitamin K in γ-carboxylation of glutamic acid in coagulation factors which are then able to bind Ca2+ and attach to the platelet phospholipid. 14  Symptoms of Vitamin K Deficiency Bruising from bleeding into the skin Nosebleeds Bleeding gums Bleeding in stomach 15 Blood in urine Blood in stool Tarry black stool Extremely heavy menstrual bleeding In infants, may result in intracranial hemorrhage  16 Severe Liver Disease  Bleeding related to liver disease when it occurs, is usually mild or moderate in degree.  Because the liver is the primary site of synthesis of most coagulation factors, severe liver disease can cause defective production of coagulation factors.  The liver does not synthesize von Willebrand factor (vWF), natural anticoagulants, and severe fibrinolytic proteins.  Liver disease impacts primary hemostasis, coagulation, and fibrinolysis  Conventional coagulation tests do not fully reflect the derangement of hemostasis and do not accurately predict bleeding risk. 17 Severe Liver Disease  Severe bleeding may be related to: a. When minor procedures, e.g. intramuscular injections, liver biopsy, etc., are performed. b. When there is a local lesion, either related to the liver disease or unrelated, e.g. peptic ulcer. c. Acute fulminating hepatitis. d. Terminal phases of chronic liver disease, especially cirrhosis.  18 Renal Disease  Chronic renal failure is associated with platelet dysfunction that results in bleeding.  When inactive coagulation factors are activated, fibrin forms and interferes with renal function, such as in DIC.  In nephrotic syndrome, low molecular weight proteins are excreted in the urine.  These include the clotting factors II, VII, IX, X, and XII and regulatory proteins, protein C and anti-thrombin.  This excretion creates thrombosis risk. 19  20 First-line tests used in investigating acute hemostatic failure 21 References  Clinical Hematology :- Theory and Procedures, Fifth Edition, by Mary Louise Turgeon  Essential Haematology: By: Hoffbrand, A. V. Malden, Mass.: Blackwell Pub., 2011.  Postgraduate Haematology: Victor Hoffbrand, Fifth Edition.  Dacie and Lewis practical haematology 10th ed., Indian ed. Author Lewis, S. M. (Shirley Mitchell).