Bleeding, Clotting & Anticoagulation

Approach: platelet-type vs factor-type bleeding

Where it bleeds tells you what failed. Defects of primary hemostasis (platelets or von Willebrand factor) cause immediate, superficial mucocutaneous bleeding: petechiae, epistaxis, gum bleeding, and menorrhagia. Defects of secondary hemostasis (coagulation factors) cause deep bleeding: hemarthroses, muscle hematomas, and delayed rebleeding after trauma or surgery.

PT is extrinsic, PTT is intrinsic. PT/INR reflects the extrinsic and common pathways; factor VII, with the shortest half-life, makes it the most sensitive test for warfarin effect and early vitamin K deficiency. PTT reflects the intrinsic pathway (factors VIII, IX, XI, XII) and monitors heparin. Mnemonic WEPT: Warfarin, Extrinsic, PT. When the PTT is prolonged, a mixing study with normal plasma sorts the cause: correction implies a factor deficiency; failure to correct implies an inhibitor, such as a lupus anticoagulant (which paradoxically causes clotting) or an acquired factor VIII inhibitor.

Thrombocytopenia: ITP, TTP, HIT, and DIC

Same number, different emergencies. Isolated bruising, schistocytes with confusion, and a platelet drop a week into heparin are three distinct diseases with opposite treatments.

ITP is a diagnosis of exclusion: isolated thrombocytopenia with an otherwise normal smear, caused by anti-platelet (GPIIb/IIIa) antibodies. In children it follows a viral illness and self-resolves; in adults it is chronic (test for HIV and hepatitis C). Children with no or skin-only bleeding are observed regardless of platelet count. Treat adults with a count below 30,000/µL or with bleeding, and children with mucosal or worse bleeding, with corticosteroids or IVIG (fastest rise), then TPO receptor agonists, rituximab, or splenectomy.

TTP comes from ADAMTS13 deficiency (usually an autoantibody), leaving ultra-large vWF multimers that trigger platelet microthrombi. The pentad is FAT RN: Fever, Anemia (microangiopathic hemolysis with schistocytes), Thrombocytopenia, Renal dysfunction, and Neurologic changes. The full pentad is often incomplete; MAHA plus thrombocytopenia is enough to act. Coagulation studies and fibrinogen are normal. Treat urgently with plasma exchange plus corticosteroids; rituximab and caplacizumab are adjuncts.

Never transfuse platelets in TTP: they fuel microthrombosis.

HIT is an IgG antibody to platelet factor 4–heparin complexes that activates platelets. Platelets fall >50% about 5–10 days after starting heparin, and the patient is prone to clot (DVT, PE, arterial thrombosis) rather than bleed, although many have thrombocytopenia alone. The PF4 antibody immunoassay screens and the serotonin release assay confirms, but act on suspicion: stop all heparin, including LMWH and flushes, and anticoagulate with argatroban, bivalirudin, fondaparinux, or, in a stable patient, a DOAC (rivaroxaban or apixaban). Isolated HIT without thrombosis still needs a non-heparin anticoagulant.

Do not start warfarin in HIT until platelets recover: protein C falls first and can cause skin necrosis or venous limb gangrene.

DIC is widespread activation of clotting (sepsis, obstetric catastrophe, malignancy, trauma) that consumes platelets and factors. Treat the underlying cause; if the patient bleeds, replace platelets, fresh frozen plasma, and cryoprecipitate for fibrinogen.

von Willebrand disease and hemophilia

von Willebrand disease is the most common inherited bleeding disorder, autosomal dominant, and causes mucocutaneous bleeding such as heavy menses and epistaxis. Because vWF carries factor VIII, the PTT may be prolonged with a normal PT; ristocetin cofactor activity is reduced. Desmopressin (DDAVP) releases stored vWF and factor VIII from endothelium and treats type 1 disease; vWF-containing concentrates and tranexamic acid cover severe types and mucosal bleeding.

Hemophilia A (factor VIII) and B (factor IX) are X-linked recessive, so affected boys have hemarthroses and deep muscle bleeds with a prolonged PTT, normal PT, normal platelets, and normal bleeding time. The mixing study corrects unless an inhibitor is present. Treat with factor replacement; mild hemophilia A can respond to desmopressin, but hemophilia B does not.

Anticoagulants: monitoring and reversal

Warfarin inhibits the vitamin K–dependent factors II, VII, IX, and X and proteins C and S and is monitored by INR (goal 2–3 for most indications, higher for mechanical mitral valves). For acute thrombosis, overlap heparin with warfarin for at least 5 days and until the INR is ≥2 for 24 hours. Reverse serious bleeding with IV vitamin K plus 4-factor prothrombin complex concentrate, which is faster and lower-volume than fresh frozen plasma. Without bleeding, a high INR is managed by holding doses, adding oral vitamin K if the INR is >10. High-thrombotic-risk patients get heparin bridging around procedures.

Heparins. Unfractionated heparin activates antithrombin, works quickly, is monitored by aPTT, and is fully reversed by protamine sulfate. Low-molecular-weight heparin (enoxaparin) acts mainly on factor Xa, is monitored by anti-Xa levels when needed, is renally cleared, and is only partially reversed by protamine. Both can cause HIT, less often with LMWH.

DOACs need no routine monitoring. Dabigatran is a direct thrombin (IIa) inhibitor reversed by idarucizumab; apixaban, rivaroxaban, and edoxaban are factor Xa inhibitors reversed by 4-factor PCC (andexanet alfa was withdrawn from the US market in December 2025).

Choosing an anticoagulant

DOACs first. DOACs are first-line for most nonvalvular atrial fibrillation and venous thromboembolism. The exceptions are high yield:

• Warfarin still wins for mechanical heart valves, antiphospholipid antibody syndrome, and severe renal impairment; DOACs are inferior and contraindicated with mechanical valves.
• LMWH is favored in pregnancy (warfarin is teratogenic) and often in active cancer.
• Non-heparin agents (argatroban, bivalirudin, fondaparinux, or a DOAC in stable patients) are required in HIT, even without thrombosis.