Lecture #161: Pathology: Hemorrhage

What are the main causes of excessive bleeding (hemorrhagic diatheses)?

Increased vessel fragility, platelet deficiency or dysfunction, and coagulation abnormalities.

What are the main steps of hemostasis?

Vasoconstriction, primary hemostasis (platelet plug), secondary hemostasis (coagulation cascade), and clot stabilization with fibrinolysis.

What is primary hemostasis?

Platelet adhesion, activation, secretion, and aggregation forming a platelet plug.

What is secondary hemostasis?

Activation of the coagulation cascade resulting in fibrin clot formation.

What is the role of tPA?

Converts plasminogen to plasmin to initiate fibrinolysis.

What is the function of plasmin?

Degrades fibrin and fibrinogen and inhibits platelet aggregation.

What is thrombocytopenia?

Platelet count <150,000/µL.

At what platelet level does spontaneous bleeding occur?

What are common clinical signs of thrombocytopenia?

Petechiae, purpura, mucosal bleeding, epistaxis, and heavy menses.

What lab findings are seen in thrombocytopenia?

Low platelets, increased bleeding time, normal PT/PTT.

What are causes of decreased platelet production?

Drugs, infections, nutritional deficiencies, aplastic anemia, marrow replacement, and myelodysplasia.

What causes increased platelet destruction?

Immune (ITP), infections, drugs, DIC, TTP, and HUS.

What is chronic immune thrombocytopenic purpura (ITP)?

Autoantibody-mediated platelet destruction targeting GpIIb/IIIa or GpIb.

What is the mechanism of platelet destruction in ITP?

IgG autoantibodies opsonize platelets leading to splenic macrophage destruction.

What is the typical presentation of chronic ITP?

Insidious onset with petechiae, purpura, easy bruising, and mucosal bleeding.

What are lab findings in chronic ITP?

Low platelets, normal PT/PTT, increased megakaryocytes in marrow.

What is the treatment for chronic ITP?

Glucocorticoids and splenectomy if severe.

What is acute ITP?

A self-limited autoimmune thrombocytopenia in children often following viral infection.

What is the presentation of acute ITP?

Sudden onset petechiae, bruising, mucosal bleeding with very low platelets.

What is the prognosis of acute ITP?

Usually resolves spontaneously within 6 months.

What is thrombotic thrombocytopenic purpura (TTP)?

A disorder of platelet microthrombi formation due to ADAMTS13 deficiency.

What is the function of ADAMTS13?

Cleaves vWF multimers to prevent excessive platelet aggregation.

What happens in ADAMTS13 deficiency?

Large vWF multimers cause platelet aggregation and microthrombi.

What is the classic pentad of TTP?

Fever, thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, and renal failure.

What lab findings are seen in TTP?

Low platelets, normal PT/PTT, schistocytes, anemia.

What is the treatment for TTP?

Plasma exchange and immunosuppression.

What is hemolytic uremic syndrome (HUS)?

A microangiopathic hemolytic anemia with thrombocytopenia and renal failure.

What causes typical HUS?

Shiga toxin from E. coli O157:H7 causing endothelial injury.

What is the triad of HUS?

Renal failure, hemolytic anemia, and thrombocytopenia.

What lab findings are seen in HUS?

Low platelets, schistocytes, renal dysfunction, normal PT/PTT.

What is the treatment for HUS?

Supportive care.

What is heparin-induced thrombocytopenia (HIT)?

Immune-mediated platelet activation due to antibodies against heparin-PF4 complexes.

Why is HIT paradoxical?

It causes thrombosis despite thrombocytopenia.

What is the management of HIT?

Stop heparin and start alternative anticoagulant.

What is Bernard-Soulier syndrome?

A platelet adhesion defect due to GpIb deficiency.

What is the key lab feature of Bernard-Soulier?

Increased bleeding time and no ristocetin-induced aggregation.

What is Glanzmann thrombasthenia?

A platelet aggregation defect due to GpIIb/IIIa deficiency.

What is the key lab feature of Glanzmann?

Normal ristocetin response but impaired aggregation with other agonists.

How does aspirin affect platelets?

Inhibits COX and TXA2 production, reducing platelet activation for lifespan of platelet.

What is uremic platelet dysfunction?

Impaired platelet adhesion and aggregation due to uremic toxins.

What is a key lab feature of platelet dysfunction?

Increased bleeding time with normal platelet count.

What characterizes coagulation factor deficiencies?

Normal platelet count with prolonged PT and/or PTT.

What is a mixing study used for?

Distinguishes factor deficiency (corrects) from inhibitor (does not correct).

What is hemophilia A?

Factor VIII deficiency, X-linked recessive.

What lab findings are seen in hemophilia A?

Prolonged PTT, normal PT.

What is a classic clinical feature of hemophilia?

Hemarthroses and deep tissue bleeding.

What is hemophilia B?

Factor IX deficiency with similar presentation to hemophilia A.

What is hemophilia C?

Factor XI deficiency, autosomal recessive, milder disease.

What is von Willebrand disease?

Defect in vWF causing impaired platelet adhesion and decreased factor VIII stability.

What are key findings in vWD?

Increased bleeding time, prolonged PTT, normal platelet count, abnormal ristocetin test.

What is disseminated intravascular coagulation (DIC)?

Widespread activation of coagulation causing thrombosis and bleeding.

What triggers DIC?

Tissue factor release or widespread endothelial injury.

What are lab findings in DIC?

Low platelets, prolonged PT/PTT, increased D-dimer, decreased fibrinogen.

What causes schistocytes in DIC?

RBC fragmentation from fibrin thrombi in microvasculature.

What is the treatment of DIC?

Treat underlying cause and provide supportive care.

What is vitamin K deficiency?

Deficiency of factors II, VII, IX, and X leading to impaired coagulation.

What lab findings are seen in vitamin K deficiency?

Prolonged PT and PTT with normal platelets.