Disorders of Hemostasis: Platelets, Coagulation & Thrombosis

Platelet disorders (ITP, Glanzmann, Bernard-Soulier) · Coagulation defects (Hemophilia A/B, von Willebrand, vitamin K deficiency) · Acquired defects · Pediatric thrombosis · Anticoagulation

🩸 Key concepts: Petechiae vs hematoma (platelet vs coagulation). PT (extrinsic) and APTT (intrinsic). Factor VIII/IX deficiency, vWD (bleeding time). Thrombophilia workup, catheter-related thrombosis, anticoagulation in children.

📖 Platelet & coagulation disorders, thrombosis in children

🩸 Platelet disorders
Quantitative: ITP (immune), TAR, Wiskott-Aldrich. Qualitative: Glanzmann thrombasthenia (GPIIb/IIIa), Bernard-Soulier (GPIb/IX), storage pool defects. Bleeding: mucocutaneous, petechiae.
🧬 Hereditary coagulation defects
Hemophilia A (FVIII), B (FIX) – X-linked, hemarthrosis, deep hematomas. von Willebrand disease (most common, autosomal, mucocutaneous + factor VIII deficiency). Rare factors (XI, VII, XIII).
⚠️ Acquired coagulation defects
Vitamin K deficiency (newborn, malabsorption), liver disease (factor synthesis), DIC (consumption), inhibitors (acquired hemophilia, lupus anticoagulant).
🩺 Thrombosis in children
Risk factors: central lines, infection, cardiac disease, trauma, thrombophilia (Factor V Leiden, prothrombin, protein C/S, antithrombin). Management: anticoagulation (LMWH, warfarin, DOACs).

⚠️ Bleeding disorder clues: Platelet type: petechiae, easy bruising, epistaxis, menorrhagia, normal PT/APTT. Coagulation factor defect: hemarthrosis, deep muscle bleeds, delayed bleeding, prolonged PT/APTT.

🩺 Diagnostic approach to bleeding & thrombosis

Bleeding phenotype – Platelet-type: petechiae, purpura, epistaxis, gum bleeding, menorrhagia (immediate). Coagulation-type: hemarthrosis, deep muscle hematomas, rebleeding after procedures, delayed bleeding.

Screening tests – CBC (platelet count), PT (extrinsic/common pathway), APTT (intrinsic pathway), bleeding time (or PFA-100). Mixing studies (corrects with normal plasma → factor deficiency; does not correct → inhibitor).

Specific assays – Factor VIII, IX, XI, von Willebrand panel (vWF:Ag, ristocetin cofactor, factor VIII), platelet aggregation studies (Glanzmann, Bernard-Soulier).

Thrombosis workup – Prothrombotic screen: Factor V Leiden, prothrombin G20210A, protein C, protein S, antithrombin, lupus anticoagulant, homocysteine. Imaging (Doppler, MRV).

📌 Clinical pearl: Hemophilia A: prolonged APTT, corrects with mixing, low factor VIII. vWD: prolonged bleeding time, low vWF antigen/ristocetin cofactor, may have low factor VIII.

📋 Management of bleeding disorders & thrombosis

Hemophilia A (severe) – Replacement factor VIII (recombinant or plasma-derived). Prophylaxis (2-3x weekly) to prevent hemarthrosis. Minor bleeds: raise to 30-50%; major/life-threatening: 80-100%. Emicizumab (bispecific antibody) for prophylaxis in hemophilia A with inhibitors.

Hemophilia B – Factor IX replacement. Higher doses (neonates, surgery). Recombinant products.

von Willebrand disease – Desmopressin (DDAVP) for type 1 (mild). Factor VIII/vWF concentrate (Humate-P) if DDAVP ineffective or type 2/3. Antifibrinolytics (tranexamic acid) for mucosal bleeding.

Immune thrombocytopenia (ITP) – Observation if mild (platelets >20, no bleeding). IVIG (1g/kg) or anti-D for significant bleeding. Corticosteroids. TPO agonists (eltrombopag) for chronic refractory.

Vitamin K deficiency bleeding (VKDB) – IM vitamin K prophylaxis at birth. Treatment: IV vitamin K ± fresh frozen plasma if severe bleeding.

Pediatric thrombosis (DVT, PE, CVST) – Anticoagulation: LMWH (enoxaparin) first-line; warfarin (monitor INR) for long-term; DOACs (rivaroxaban) increasingly used. Treat underlying risk factor (remove line).

🚨 Emergency in hemophilia: Intracranial bleed, neck hematoma, severe hemarthrosis. Immediate factor replacement to 100% (FVIII or FIX). Avoid IM injections, NSAIDs.

🧠 Reflex prompts: hemostasis & thrombosis

🩸 Boy with recurrent knee hemarthrosis, easy bruising. PT normal, APTT prolonged, corrects on mixing. Most likely diagnosis?
Hemophilia A (factor VIII deficiency). Factor VIII assay <1%. Prophylaxis with factor VIII.
🩺 Child with epistaxis, gum bleeding, family history of bleeding. Platelets normal, PT normal, APTT mildly prolonged, bleeding time prolonged. Likely?
von Willebrand disease (type 1). DDAVP trial. vWF panel confirms.
🩸 Newborn with bleeding from circumcision. PT and APTT prolonged. Maternal history of epilepsy on phenytoin. Most likely?
Vitamin K deficiency bleeding. Preventable with IM vitamin K. Treat with IV vitamin K + FFP.
🩺 5-year-old with sudden petechiae, platelets 8000, otherwise well. Most likely?
Immune thrombocytopenia (ITP). IVIG or observation. Bone marrow if atypical.
🧬 Teenager with recurrent DVT, family history of thrombosis. Factor V Leiden heterozygous. Next step?
Anticoagulation for acute event (LMWH/warfarin). Thrombophilia workup. Counsel on risk factors.
🩸 Child with prolonged bleeding after tooth extraction, PT normal, APTT prolonged, mixing study does NOT correct. Diagnosis?
Inhibitor (e.g., factor VIII inhibitor, lupus anticoagulant). Bethesda assay for FVIII inhibitor.
🧬 Which coagulation factor deficiency is X-linked?
Hemophilia A (FVIII) and hemophilia B (FIX). Also X-linked thrombocytopenia (WAS).
🩸 Most common inherited bleeding disorder?
von Willebrand disease (autosomal, ~1% population).
🩺 What is the first-line prophylaxis for hemophilia A without inhibitors?
Recombinant factor VIII (2-3 times weekly) to prevent hemarthrosis and joint damage.
🩸 Child with catheter-related DVT. Anticoagulation of choice in neonate/infant?
LMWH (enoxaparin) – titrate to anti-Xa level (0.5-1). Warfarin avoided in neonates.