Heme Lecture 4 - Hemostasis & Coagulation Disorders

Flashcards covering essential topics and concepts on Hemostasis and Coagulation Disorders.

What is hemostasis?

Cessation of bleeding through vascular spasm, platelet plug formation, and coagulation cascade.

What are the three main phases of hemostasis?

(1) Vascular spasm (2) Platelet plug (primary hemostasis) (3) Coagulation cascade (secondary hemostasis).

What happens during tertiary hemostasis?

Activation of coagulation inhibitors to limit clot size and fibrinolysis for clot breakdown after repair.

What are the two initiating pathways of coagulation?

Intrinsic (cell surface damage) and extrinsic (tissue factor release).

What do both intrinsic and extrinsic pathways converge on?

Common pathway → formation of prothrombin activator → thrombin → fibrin clot.

Which is faster: intrinsic or extrinsic pathway?

Extrinsic (tissue factor-mediated).

Which factors are vitamin K-dependent?

II, VII, IX, X, C, S.

What triggers the intrinsic pathway?

Contact with damaged endothelium or collagen.

What factors are involved in the intrinsic pathway?

XII, XI, IX, VIII, X, V, II, I (fibrinogen).

What triggers the extrinsic pathway?

Tissue trauma → tissue thromboplastin (Factor III) → activates Factor VII.

What factors are common to both pathways?

X, V, II (prothrombin), I (fibrinogen).

What does PT (Prothrombin Time) test?

Extrinsic and common pathways – factors II, V, VII, X, fibrinogen.

What does a prolonged PT suggest?

Deficiency or inhibition of extrinsic/common factors (e.g., vitamin K deficiency, liver disease, warfarin use).

What does PTT (Partial Thromboplastin Time) test?

Intrinsic and common pathways – factors II, V, VIII, IX, X, XI, XII.

What does a prolonged PTT indicate?

Intrinsic pathway defect (e.g., hemophilia, vWD).

What is the purpose of a mixing study?

Distinguishes deficiency vs inhibitor: correction = deficiency, no correction = inhibitor.

What causes Hemophilia A?

Factor VIII deficiency.

What causes Hemophilia B?

Factor IX deficiency (Christmas disease).

What is the inheritance pattern of hemophilias?

X-linked recessive – affects males.

What is a typical lab finding in hemophilia?

Prolonged PTT, normal PT and platelets.

What are the clinical features of hemophilia?

Deep muscle/joint hemorrhage, intracranial bleed, post-surgical bleeding.

What is the treatment of Hemophilia A and B?

Recombinant factor replacement, DDAVP (A only), antifibrinolytics, gene therapy.

What causes acquired factor deficiency?

Autoantibodies or alloantibodies inhibiting coagulation factors.

Which factor inhibitor is most common?

Factor VIII inhibitor.

What is a lab clue for acquired factor inhibitor?

Prolonged PTT that does NOT correct with mixing study.

What is the treatment for acquired factor deficiency?

High-dose factor replacement, FEIBA, or NovoSeven.

Which factors are decreased in vitamin K deficiency?

II, VII, IX, X.

What are the lab findings for vitamin K deficiency?

Prolonged PT/PTT, elevated liver enzymes.

What is the treatment for vitamin K deficiency?

Parenteral vitamin K, FFP if bleeding.

What is the most common inherited bleeding disorder?

Von Willebrand Disease (vWD).

What is the function of von Willebrand factor (vWF)?

Binds platelets to endothelium, platelets to each other, and stabilizes Factor VIII.

What is the inheritance pattern of vWD?

Autosomal dominant.

What is a typical presentation of vWD?

Mucocutaneous bleeding – epistaxis, menorrhagia, easy bruising.

What labs are for vWD?

vWF antigen, activity (RCo, CB), and Factor VIII assays.

What is the treatment of vWD types?

Type 1 – DDAVP; Type 2 – vWF concentrate; Type 3 – vWF concentrate only.

What is DIC?

Pathologic activation of coagulation and fibrinolysis → consumption of platelets and factors → bleeding + thrombosis.

What are the major triggers of DIC?

Sepsis, trauma, malignancy, obstetric complications, snakebite.

What are the lab findings in DIC?

↑ D-dimer, ↓ fibrinogen, ↓ platelets, ↑ PT/PTT, ↓ protein C.

What is the treatment for DIC?

Treat underlying cause, supportive care, replace platelets/FFP if bleeding.

What does HELLP stand for?

Hemolysis, Elevated Liver enzymes, Low Platelets.

When does HELLP occur?

Third trimester, often with preeclampsia/eclampsia.

What are the complications of HELLP?

DIC (30%), placental abruption, renal failure.

What is TTP?

Thrombotic thrombocytopenic purpura – platelet destruction, neurologic sx > renal.

What is HUS?

Hemolytic uremic syndrome – renal failure > neurologic sx.

What is a common cause of HUS in kids?

E. coli O157:H7.

What is the treatment for both TTP and HUS?

Plasma exchange (plasmapheresis), supportive.

What is Virchow’s triad?

Endothelial injury, stasis, hypercoagulability.

What are the two types of thrombosis?

Venous (stasis-related) and arterial (platelet-rich).

What are acquired hypercoagulable states?

HIT, antiphospholipid syndrome, malignancy, pregnancy, immobility, trauma.

What are inherited hypercoagulable states?

Factor V Leiden, Protein C/S deficiency.

What mutation causes Factor V Leiden?

Arg506Gln → resistance to activated Protein C.

What is the lab test for Factor V Leiden?

DNA test or APC-resistance assay.

What is the treatment of hypercoagulable states/VTE?

Anticoagulation (heparin → warfarin or DOACs). Duration depends on cause.

What is the mechanism of heparin?

Potentiates antithrombin → inhibits factor II and Xa.

What is the mechanism of warfarin?

Inhibits vitamin K–dependent factor synthesis.

What is the monitoring for warfarin?

PT/INR (goal 2–3).

What is the reversal of warfarin?

Vitamin K, FFP, or prothrombin complex concentrates.

What are the Direct oral anticoagulants (DOACs)?

Rivaroxaban, apixaban (Xa inhibitors), dabigatran (direct thrombin inhibitor).

What is an advantage of DOACs?

No lab monitoring, fewer food interactions.

What is a major risk with DOACs?

Increased bleeding.

What is the mechanism of tPA?

Converts plasminogen → plasmin → clot lysis.

What are the main indications for thrombolytics?

Acute MI, ischemic stroke, arterial occlusion (not typically VTE).

What is a major risk of thrombolytics?

Serious bleeding and re-thrombosis.

What is the pathophysiology of HIT?

Immune complex activates platelets → thrombosis despite thrombocytopenia.

What is the key mechanism in HIT?

Anti-PF4 antibodies activate FcγRIIA receptors on platelets and endothelium.

What are the resulting effects of HIT?

Platelet activation, endothelial injury, ↑ tissue factor expression → thrombosis.

What is the main concern with acute blood loss?

Hypovolemic shock and decreased O₂ delivery.

What is the CV reflex response to blood loss?

Vasospasm to maintain perfusion.

What solutions can expand volume rapidly?

Ringer’s lactate, normal saline (3–4 L for 1 L expansion).

What is FFP used for?

Replaces clotting factors during massive transfusion.

What can FFP cause as a side effect?

IgE-mediated allergic reaction.

What is primary hemostasis?

Platelet plug.

What is secondary hemostasis?

Fibrin clot.

What are the intrinsic factor deficiencies in Hemophilia A/B?

Factor VIII/IX deficiencies.

What is the most common inherited bleeding disorder?

vWD.

What is impaired in vWD?

Impaired platelet adhesion.

What does DIC lead to?

Uncontrolled coagulation + fibrinolysis → bleeding + thrombosis.

How do TTP and HUS differ?

Both microangiopathies; TTP = neuro, HUS = renal.

What is a common inherited cause of thrombosis?

Factor V Leiden.

What are the anticoagulants?

Heparin (IIa/Xa), warfarin (vit K), DOACs (Xa or IIa).