How bleeding disorders are tested on Step 1

Read the lab pattern first, then the clinical clue.

DisorderPlateletsBleeding timePTPTT
ITP↓↑NormalNormal
TTP / HUS↓↑NormalNormal
DIC↓↑↑↑
Von Willebrand diseaseNormal↑NormalNormal or ↑
Hemophilia A or BNormalNormalNormal↑
Vitamin K deficiency, warfarinNormalNormal↑Normal or ↑
Bernard-Soulier↓ (giant platelets)↑NormalNormal
Glanzmann thrombastheniaNormal↑NormalNormal

PT tests the extrinsic and common pathways (factor VII); PTT tests the intrinsic and common pathways (factors VIII, IX, XI, XII).

Platelet disorders

Name the step that fails: adhesion, aggregation, or survival.

Bernard-SoulierGpIb missing; no adhesion to vWF; large platelets;ristocetin test abnormalVon WillebrandvWF low or defective; ristocetin abnormal, correctswith normal plasmaGlanzmannGpIIb/IIIa missing; no aggregation; ristocetin testnormalAspirin, uremiaAcquired dysfunction; aspirin irreversibly blocksCOX-1 and TXA2
Platelet function. vWF also carries factor VIII, which is why severe vWD can prolong the PTT.
ITPIgG against GpIIb/IIIaPlatelets destroyed in spleenOtherwise well; no hemolysisChildren after viral illness; adultschronicSteroids, IVIG; splenectomy ifrefractoryTTPAntibody against ADAMTS13 (usually)Large vWF multimers form microthrombiSchistocytes, ↑ LDH, ↓ haptoglobinFever, confusion, kidney injuryUrgent plasma exchangevs
ITP vs TTP. HUS looks like TTP with dominant kidney failure, classically after Shiga toxin-producing E. coli O157:H7 in children.

Coagulation factor and consumptive disorders

Mixing studies separate a deficiency from an inhibitor.

  • Hemophilia A and B: X-linked deficiency of factor VIII or IX; hemarthrosis and bleeding after surgery. A mixing study corrects the PTT; an inhibitor (or lupus anticoagulant) does not.
  • Vitamin K deficiency: newborns without prophylaxis, malabsorption, broad-spectrum antibiotics; factors II, VII, IX, X fall, and PT rises first.
  • DIC: triggered by sepsis, trauma, obstetric complications, acute promyelocytic leukemia, or snake bites; schistocytes, low fibrinogen, high D-dimer.
  • Heparin-induced thrombocytopenia: IgG against heparin–platelet factor 4 complexes 5–10 days after heparin; platelets fall but patients clot. Stop all heparin and start a non-heparin anticoagulant such as argatroban.

Inherited thrombophilias

Suspect them with clots at a young age, unusual sites, or a strong family history.

DisorderMechanismClue
Factor V LeidenFactor V resists inactivation by activated protein CMost common inherited thrombophilia in people of European descent
Prothrombin G20210AIncreased prothrombin levelsVenous clots
Protein C or S deficiencyLess inactivation of factors Va and VIIIaWarfarin-induced skin necrosis
Antithrombin deficiencyLess inhibition of thrombin and factor XaHeparin has little effect on PTT
Antiphospholipid syndrome (acquired)Autoantibodies (lupus anticoagulant, anticardiolipin)Clots, recurrent pregnancy loss; PTT prolonged in vitro

Virchow triad: stasis, endothelial injury, and hypercoagulability.

Worked example

Use the mixing study.

functions Worked example — a swollen knee after a fall

A 7-year-old boy has a hot, swollen knee after a minor fall. His maternal uncle had similar episodes. Platelet count and PT are normal; PTT is prolonged and corrects when mixed with normal plasma. What is the diagnosis?

  1. Bleeding into a joint suggests a coagulation factor problem rather than a platelet problem.
  2. An isolated prolonged PTT points to the intrinsic pathway (factors VIII, IX, XI, XII).
  3. Correction with normal plasma means a missing factor, not an inhibitor.
  4. Affected maternal male relatives suggest X-linked inheritance: factor VIII (or IX) deficiency.

Answer. Hemophilia A (factor VIII deficiency) is most likely; check factor VIII and IX levels.