Bleeding Disorders PDF

Bleeding Disorders Karen Gil MD, MHSN Bleeding Disorders Characterized by abnormal bleeding Appear spontaneously or follow an event (trauma or surgery) Normal clotting involves the vessel wall, platelets and clothing factors Any abnormalities in any of these components Schematic of the blood coagula...

Bleeding Disorders Karen Gil MD, MHSN Bleeding Disorders Characterized by abnormal bleeding Appear spontaneously or follow an event (trauma or surgery) Normal clotting involves the vessel wall, platelets and clothing factors Any abnormalities in any of these components Schematic of the blood coagulation cascade. Activation of the coagulation cascade triggers the conversion of the inactive coagulation factors (represented by an F followed by a Roman number, e.g., FXII) to their active form (FXIIa) by a series of enzymatic reactions. The intrinsic pathway (purple) is also termed the “contact activation pathway,” which is activated by negatively charged surfaces, such as polyphosphates. The extrinsic pathway (orange) is initiated by TF that is released during vascular injury. The activation of platelets upon injury is not depicted here. The activation of coagulation factor ten (FX) marks the start of the common pathway (green) that leads to the formation of cross-linked fibrin clots. Bleeding Disorders Lab Test PT – Prothrombin time Measures the time needed for plasma to clot Measures the integrity of extrinsic pathway Normal 11-13.5 seconds Causes of prolonged PT Deficiency of factor V, VII, or X Deficiency of prothrombin Deficiency of fibrinogen Acquired inhibitor as an antibody that interferes with extrinsic pathway Bleeding Disorders Lab Test PTT – Partial thromboplastin time Measures the time needed for the plasma to clot Normal 25-35 Prolonged PTT causes Deficiency of factor V, VII, IX, X, XI, XII Deficiency of prothrombin Deficiency of fibrinogen Acquired inhibitors of intrinsic pathway Bleeding Disorders Lab Test Platelet count CBC 150,000 to 450,000 /µl Platelet aggregation Measure the response of platelets von Willebrand Factor between 50 and 200 IU/dl Levels below 50 are low Thrombocytopenia Deficiency of platelets Blood smear test Cause Bleeding Thrombocytopenia Purpura- Easy or excessive bruising Petechiae Superficial bleeding into the skin that appears as a rash of pinpoint-sized reddish-purple spots usually on the lower limbs Prolonged bleeding from cuts Bleeding from gums epistaxis Hematuria Blood in stools Unusually heavy menstrual periods Fatigue Splenomegaly Bleeding Disorders Major causes of acquired coagulation disorders Disseminated intravascular coagulation (DIC) Liver disease (cirrhosis, hepatitis, fatty liver) Coagulation factors are made in the liver by hepatocytes Vitamin K deficiency Most common hereditary disorders of hemostasis von Willebrand disease Most common hereditary coagulation disorders Hemophilias Disseminated Intravascular Coagulation Disorder (DIC) Abnormal, excessive generation of thrombin and fibrin in the circulating blood During the disease increase platelet aggregation and coagulation factor consumption occur Evolve slowly (weeks or months) Characterized by Bleeding Vascular occlusion (thrombosis) and/or tissue hypoxemia Disseminated Intravascular Coagulation Disorder Common triggers Sepsis Major trauma (surgery, burns, trauma) Certain cancers Obstetric complications Prolonged PT and PTT with thrombocytopenia Disseminated Intravascular Coagulation Disorder Symptoms of DIC may include any of the following: Bleeding, from many sites in the body Blood clots Bruising Drop in blood pressure Shortness of breath Confusion, memory loss or change of behavior Fever Treatment Treat the cause Replacement of platelets Plasma (include coagulation factor and fibrinogen) Immune Thrombocytopenia Purpura (ITP) Caused by autoantibodies against platelet antigens Chronic in adults, acute and self-limited in children May be triggered by Drugs Infection Lymphomas Idiopathic Clinical findings Normal spleen size Exclude other causes as HIV, hepatitis C Immune Thrombocytopenia Purpura (ITP) Medicine Classification Examples of Implicated Medicines Antibiotics Cephalosporins, penicillins, sulphonamides, trimethoprim, vancomycin Antimalarials Quinine Antimycobacterials Ethambutol, rifampicin Antiepileptics Carbamazepine, phenytoin, sodium valproate NSAIDs Ibuprofen, naproxen Cardiovascular drugs amiodarone, furosemide, quinidine, thiazides Vaccines Diphtheria, Tetanus, Pertussis (DTaP), Haemophilus influenzae type B, Influenza, MMR, pneumococcal, varicella zoster Others Haloperidol, Acetaminophen Immune Thrombocytopenia Purpura (ITP) Symptoms of ITP skin that bruises very easily Petechiae bleeding from any area of the body bleeding from the gums epistaxis that take a long time to stop internal bleeding long or heavy menstrual periods Treatment Corticosteroids Splenectomy Immunosuppressants Platelet transfusions Von Willebrand Disease Autosomal dominant disorder caused by mutations in vWF A large protein that promotes the adhesion of platelets Signs and Symptoms Excessive bleeding after a surgery Prolonged and heavy menstrual periods Epistaxis takes more 10 min to stop Heavy bleeding during labor and delivery Easy bruising Hematuria Blood in stools vWF serves as a carrier of factor VIII and promote platelet binding Von Willebrand Disease Typically causes a mild to moderate bleeding Screening test show normal platelet count, slightly prolonged PTT Factor VIII Clotting activity decrease von Willebrand factor antigen low levels Treatment: Desmopressin IV or intranasal Antidiuretic action Shortness the bleeding time Hemophilia Hemophilia A X-linked disorder caused by mutations in factor VII Affects commonly males Severe bleeding into soft tissues and joints Prolonged PTT with normal platelets and PT Hemophilia B X-linked disorder caused by mutations in coagulation factor IX Severe bleeding into soft tissues and joints Prolonged PTT with normal platelets and PT Treatment Replacement of the deficient factor IV