Hypocoagulable disorders Notes

NOTES NOTES HYPOCOAGULABLE DISORDERS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Acquired, inherited disorders; defects in coagulation cascade SIGNS & SYMPTOMS ▪ Bleeding ▪ Thrombosis, only disseminated intravascular disease (DIC) DIAGNOSIS LAB RESULTS ▪ ▪ ▪ ▪ ▪ ▪ Platelet count Levels of clotting factors Prothrombin time (PT) Partial thromboplastin time (aPTT) Fibrin degradation products Genetic testing TREATMENT OTHER INTERVENTIONS ▪ Supportive therapy DISSEMINATED INTRAVASCULAR COAGULATION (DIC) osms.it/disseminated-intravascular-coagulation PATHOLOGY & CAUSES ▪ Acquired, paradoxical process of thrombosis, bleeding ▪ Release of procoagulants, tissue factors, bacterial components, enzymes/major endothelial injury → excessive activation of coagulation cascade → thrombosis of small/medium blood vessels → activation of fibrinolysis to resolve clots → fibrin degradation products released into circulation → interfere with platelet aggregation, clot formation ▪ Depletion of platelets, fibrin, coagulation factors → consumption coagulopathy CAUSES ▪ Complication of underlying conditions ▪ Obstetric complications (e.g. preeclampsia, obstetric hemorrhage, retained dead fetus) ▪ Critical illness (individuals in intensive care unit) ▪ Malignancy ▫ Mucin-secreting adenocarcinoma (e.g., lungs, pancreas, stomach, prostate, ovaries) ▫ Acute promyelocytic leukemia (APL) ▪ Infection/sepsis, especially gram-negative bacteria ▪ Massive tissue injury due to trauma, OSMOSIS.ORG 389

surgery, burn, fracture ▪ Intravascular hemolysis due to blood type incompatibility ▪ Shock ▪ Snakebites COMPLICATIONS ▪ Widespread thrombosis, ischemia, necrosis of brain, heart, kidneys, liver, lungs, adrenals, spleen → organ dysfunction ▪ Microangiopathic hemolytic anemia (MAHA) ▪ Paradoxical tendency to life-threatening bleeding, due to consumption of procoagulatory factors MNEMONIC: DIC TEAR Common causes of DIC Delivery TEAR: obstetric complications Infections: gram negative)/ Immunological Cancer: prostate, pancreas, lung, stomach Obstretrical complications Toxemia of pregnancy Emboli (amniotic) Abruptio placentae Retain fetus products SIGNS & SYMPTOMS ▪ Acute: bleeding episodes (e.g. ecchymoses, petechiae, purpura, blood oozing from gingival/oral mucosa, sites of trauma, catheters, intravenous lines) ▪ Chronic: thromboembolism, tissue hypoxia, infarctions DIAGNOSIS LAB RESULTS ↓ Platelets ↓ Fibrinogen ↓ Clotting factors ↑ Prothrombin time (PT) ↑ Partial thromboplastin time (aPTT) ↑ D-dimers (fibrin degradation product) Schistocytes, damaged red blood cells (RBCs) due to MAHA ▪ Physiologic compensation → lab results normal ▫ For chronic (solid tumors, large aortic aneurysms) ▪ ▪ ▪ ▪ ▪ ▪ ▪ TREATMENT MEDICATIONS ▪ Oxygen, IV fluids OTHER INTERVENTIONS ▪ Replace clotting factors with fresh frozen plasma (FFP), cryoprecipitate, fibrinogen ▪ Platelet transfusions, if platelet count < 30,000 ▪ RBC transfusions for severe bleeding 390 OSMOSIS.ORG

Chapter 47 Hypocoagulable Disorders HEMOPHILIA A osms.it/hemophilia-a PATHOLOGY & CAUSES ▪ Most common inherited clotting factor deficiency; classic hemophilia ▪ X-linked recessive disorder ▪ Mutated gene F8 on X chromosome CAUSES ▪ Quantitative/qualitative deficiency of factor VIII → insufficient activation of the intrinsic pathway → defect in common coagulation pathway → increased tendency for bleeding ▪ Peritoneal dialysis RISK FACTORS ▪ More common in individuals who are biologically male; individuals who are biologically female more likely to be carriers SIGNS & SYMPTOMS ▪ Varies according to mutation, factor VIII activity ▪ Asymptomatic/spontaneous bleeding ▪ < 10% factor VIII ▫ Easy bruising ▫ Prolonged bleeding, after injury/surgery ▫ Hematomas (e.g. muscle hematomas, hemophilic pseudotumors) ▫ Gastrointestinal (GI) bleeding ▫ Hematuria ▫ Severe epistaxis ▫ Painful hemarthrosis → progressive joint irregularity, disability (knee most common) ▫ Intracerebral hemorrhage DIAGNOSIS LAB RESULTS ▪ Normal platelet count ▪ Normal prothrombin time (extrinsic pathway not affected) ▪ Prolonged partial thromboplastin time (intrinsic pathway affected) ▪ Factor VIII clotting assay ▪ Genetic testing TREATMENT MEDICATIONS Desmopressin (DDAVP) ▪ For mild quantitative hemophilia A ▫ → stimulates von Willebrand factor (vWF) release → promotes stabilization of residual factor VIII OTHER INTERVENTIONS ▪ Recombinant factor VIII infusions ▪ If severe deficiency, immune system may perceive supplemental factors as foreign → production of antibodies (inhibitors) → elimination of injected factors/anaphylaxis ▪ Avoid sports, trauma, medications that promote bleeding ▪ Local measures ▫ Treat hemarthrosis, hematomas (e.g. resting of affected part, application of ice) OSMOSIS.ORG 391

Figure 47.1 An abdominal MRI scan in the coronal plane demonstrating a hematoma of the right psoas muscle in an individual with hemophilia. Figure 47.2 An MRI scan of the knee demonstrating hemarthrosis. Individuals with hemophilia are at increased risk of hemarthrosis. HEMOPHILIA B osms.it/hemophilia-b PATHOLOGY & CAUSES DIAGNOSIS ▪ Mutated gene F9 on X chromosome ▪ AKA Christmas disease ▪ Qualitative/quantitative deficiency of coagulation factor IX → insufficient activation of intrinsic coagulation pathway → impaired hemostasis ▪ Less common LAB RESULTS SIGNS & SYMPTOMS MEDICATIONS ▪ Spontaneous bleeding, delayed bleeding after trauma, hemarthrosis, hematomas, epistaxis, intracranial, GI/genitourinary tract bleeding ▪ Normal platelet count, prothrombin time (intrinsic pathway affected) ▪ Factor IX clotting assay/genetic mutation testing TREATMENT DDAVP ▪ Not helpful in hemophilia B; stimulates vWF → stabilizes only factor VIII, not IX OTHER INTERVENTIONS ▪ Infusions of recombinant factor IX 392 OSMOSIS.ORG

Chapter 47 Hypocoagulable Disorders VON WILLEBRAND DISEASE osms.it/von-willebrand-disease PATHOLOGY & CAUSES ▪ Most common inherited bleeding disorder of primary hemostasis ▪ Defective platelet function with normal platelet count ▪ Quantitative/qualitative deficiency of vWF → impaired platelet aggregation, adhesion, dysfunction of factor VIII → deficiency in coagulation cascade → bleeding tendency ▪ Hemostatic pressure (e.g. surgery/trauma) TYPES Type I ▪ Most common ▪ Autosomal dominant, partial quantitative deficiency Type II ▪ Autosomal dominant, qualitative deficiency Type III ▪ Autosomal recessive, severe quantitative deficiency SIGNS & SYMPTOMS DIAGNOSIS LAB RESULTS Abnormal PFA-100 test ↓ factor VIII activity ↓ vWF PTT prolonged ↓ platelet aggregation, presence of ristocetin ▪ Collagen-binding function reduced ▪ Platelet count normal ▪ ▪ ▪ ▪ ▪ TREATMENT MEDICATIONS ▪ DDAVP ▫ Type I, Type II ▪ Factor VIII/vWF concentrates ▫ After major injury; during operation; Type III, II not responding to DDAVP ▪ High-purity vWF concentrates OTHER INTERVENTIONS ▪ Local measures, tranexamic acid for mild bleeding ▪ Typically asymptomatic ▪ Surgery/trauma provoke clinical manifestation ▪ Spontaneous mucosal, cutaneous bleeding (e.g. epistaxis, easy bruising, excessive bleeding from wounds, bleeding gums) ▪ Menorrhagia ▪ GI bleeding ▪ Internal/joint bleeding (Type III) OSMOSIS.ORG 393