The question isn't "what's wrong?" It's "which STEP is broken?" Get this wrong and you'll confuse hemophilia with everything else.
The Setup
9-year-old boy. Knee swelling after soccer collision. History of prolonged bleeding after tooth extraction. Multiple bruises in various stages. Labs: platelets 235k (normal), PTT 78 sec (HIGH), PT 14 sec (normal), bleeding time 4 min (normal).
Which step in coagulation is most likely directly affected?
The Pattern
Read the Labs, Find the Pathway
The one rule that governs this entire topic:
PTT tests the intrinsic pathway. PT tests the extrinsic pathway. If only one is prolonged, you know exactly which half of the cascade is broken.
This kid: PTT is sky-high. PT is normal. Platelets are normal. Bleeding time is normal. That means:
✓ Primary hemostasis (platelets, vWF) is working fine.
✓ Extrinsic pathway is fine.
✗ Intrinsic pathway is broken.
🔑PTT = Pathway that's Intrinsic (the P points In). PT = Pathway that's Extrinsic (the T points ouT).
The Cascade
Three Pathways, One Bottleneck
Intrinsic Pathway (PTT)
Contact activation (XII → XIIa)
↓
XI → XIa
↓
IX → IXa ⚠ Hemophilia B = missing factor IX
↓
VIIIa + IXa complex ⚠ Hemophilia A = missing factor VIII
↓ This complex converts...
Factor X → Factor Xa ← THIS is the step that's impaired
Extrinsic Pathway (PT)
Tissue factor + VII → VIIa
↓ This ALSO converts...
Factor X → Factor Xa ← Still works! (PT is normal)
⚡Factor X can be activated by BOTH pathways. Hemophilia blocks the intrinsic route to factor X (via VIII/IX), but the extrinsic route (via VII) still works. That's why the PT stays normal.
Step Through
Walk the Cascade, Step by Step
Tap "Next Step" to advance. Watch where Hemophilia A and Hemophilia B break the chain.
Extrinsic · PT
Tissue damage exposes tissue factor (TF / III)
↓
TF + VII → VIIa
↓ activates X
Intrinsic · PTT
Contact activation: XII → XIIa
↓
XI → XIa
↓
IX → IXa · Hemophilia B blocks here
↓
VIIIa + IXa tenase complex · Hemophilia A blocks here
↓ activates X
Common
X → Xa (joined by Va)
↓
Prothrombin (II) → Thrombin (IIa)
↓
Fibrinogen (I) → Fibrin
↓
XIII cross-links fibrin into a stable clot
Press Next Step to start at the trigger.
vWF connection: Von Willebrand factor carries factor VIII in plasma. Without vWF, factor VIII gets cleared fast and PTT goes up. That is why vWD also elevates PTT, and why severe vWD looks like mild Hemophilia A on labs.
Step 0 / 10
⚠️
Board trap: PTT elevated, PT normal
Isolated PTT up with normal PT = intrinsic pathway defect. The differential is short: factor VIII (Hemophilia A), factor IX (Hemophilia B), factor XI (Hemophilia C), factor XII (no bleeding), vWD, lupus anticoagulant, or heparin. Bleeding pattern + mixing study sorts them.
Factor X Bottleneck
Why "Conversion of Factor X" Is the Answer
The question doesn't ask "what factor is missing?" It asks "which STEP is affected."
Hemophilia A = missing factor VIII. Hemophilia B = missing factor IX. Both VIII and IX form a complex that converts factor X to Xa. Without that complex, the intrinsic pathway can't activate factor X.
The step is: conversion of factor X. Not "production of factor VIII." Not "formation of thrombin." The specific enzymatic reaction that's impaired.
⚠️
Trap: "Formation of Thrombin"
Thrombin formation happens in the COMMON pathway (Xa + Va → thrombin). Once factor X gets activated by the extrinsic pathway, the common pathway works fine. Hemophilia doesn't directly impair thrombin formation. It impairs the step BEFORE the common pathway.
⚠️
Trap: Hemophilia vs von Willebrand Disease
Both have prolonged PTT. Both have normal PT. The difference? Bleeding time. vWD = prolonged bleeding time (platelets can't stick). Hemophilia = normal bleeding time (platelets work fine, it's the clot that's weak). Also: vWD = mucosal bleeding (nosebleeds, gum bleeding, heavy periods). Hemophilia = deep bleeding (hemarthrosis, muscle hematomas).
⚠️
Trap: "Activation of Factor VII"
Factor VII is the extrinsic pathway. If VII were the problem, PT would be prolonged and PTT would be normal. This kid has the opposite pattern. The extrinsic pathway is untouched.
Lab Patterns
Know the Pattern, Know the Diagnosis
Condition
PTT
PT
BT
Platelets
See It
Hemophilia A/B
↑
Normal
Normal
Normal
Hemarthrosis, deep bleeds
vWD
↑
Normal
↑
Normal
Mucosal bleeds, menorrhagia
Factor VII deficiency
Normal
↑
Normal
Normal
Only extrinsic pathway affected
DIC
↑
↑
↑
↓
Schistocytes, elevated D-dimer
ITP
Normal
Normal
↑
↓
Petechiae, anti-platelet Ab
Liver failure
↑
↑
Normal
Normal/↓
All factors made in liver
The High-Yield Detail
Hemophilia A is X-linked recessive. That means it almost exclusively affects males. But here's the thing: 30% of hemophilia A cases are new mutations with no family history. So when a boy shows up with hemarthrosis and a sky-high PTT, don't let "no family history" throw you off. One in three is brand new.
Same Pattern, Different Disease
The "PTT up, PT normal" pattern isn't just hemophilia. It's any intrinsic pathway problem: factor XII deficiency (asymptomatic!), factor XI deficiency (hemophilia C, Ashkenazi Jewish), lupus anticoagulant (paradoxically causes CLOTTING, not bleeding). The lab pattern is the same. The clinical picture tells you which one.
🔑Hemophilia = Hemarthrosis + High PTT + Hereditary (X-linked). Three H's.
Clinical Vignettes
Test Yourself
Read the labs. Find the pathway. Name the step.
The cascade is clicking.
The Lineup
Factor Deficiencies & Coagulopathies
Tap to flip.
🧬
Hemophilia A
Factor VIII deficiency. X-linked recessive.
Tap to flip
Hemophilia A
Defect: Factor VIII deficiency
Inheritance: X-linked recessive
Severity: Severe if <1% activity
Labs: aPTT up, PT normal
Bleeding: Hemarthrosis, deep tissue bleeds
Board pearl: 30% are new mutations, no family history
🩺
Hemophilia B
Christmas disease. Factor IX deficiency. X-linked recessive.
Tap to flip
Hemophilia B (Christmas Disease)
Defect: Factor IX deficiency
Inheritance: X-linked recessive
Labs: aPTT up, PT normal (identical to Hemophilia A)
Distinguish: Factor IX assay
Treatment: Recombinant FIX concentrate; NOT DDAVP
✡️
Hemophilia C
Factor XI deficiency. Autosomal recessive. Ashkenazi Jewish.
Tap to flip
Hemophilia C (Factor XI Deficiency)
Defect: Factor XI deficiency
Inheritance: Autosomal recessive
Population: Ashkenazi Jewish
Bleeding: Surgical-related, NOT spontaneous hemarthrosis
Board pearl: Variable severity; aPTT up but bleeding poorly correlates with level
🔬
Factor XII Deficiency
Hageman factor. Prolonged aPTT in lab. Zero bleeding. Thrombosis risk.
Tap to flip
Factor XII Deficiency (Hageman)
Defect: Factor XII (contact activation)
Labs: aPTT markedly prolonged
Clinical: NO bleeding whatsoever
Paradox: Thrombosis risk instead
Board pearl: Prolonged aPTT with zero clinical bleeding = think Factor XII first
🥦
Vitamin K Deficiency
Blocks II, VII, IX, X, protein C/S. PT rises first (FVII shortest half-life).
Tap to flip
Vitamin K Deficiency
Blocks: Factors II, VII, IX, X, Protein C and S
Labs: PT up AND aPTT up
Why PT first: Factor VII has the shortest half-life (6h)
Treatment: Treat underlying cause; FFP/cryo/platelets as needed
Board pearl: Consumption of ALL factors + platelets = everything is off
🩸
Factor V Leiden
Resistance to APC. Most common hereditary thrombophilia. Clots, not bleeding.
Tap to flip
Factor V Leiden
Defect: Factor V mutated, resistant to activated protein C (APC)
Result: Thrombosis, not bleeding
Most common: Hereditary thrombophilia in Western populations
Risk: DVT, PE, especially with OCPs or pregnancy
Board pearl: Labs may show aPTT prolonged but CLOTS in vivo
⚡
Antiphospholipid Syndrome
Lupus anticoagulant. Clots in vivo, prolonged aPTT in vitro.
Tap to flip
Antiphospholipid Syndrome
Antibodies: Anti-cardiolipin, lupus anticoagulant, anti-beta-2-glycoprotein I
Labs: aPTT prolonged in vitro, mixing study does NOT correct
Clinical: CLOTS (DVT, PE, stroke) NOT bleeding
OB: Recurrent pregnancy loss (placental thrombosis)
Board pearl: Triple paradox: not just lupus, not an anticoagulant, clots not bleeds
Decision Tree
Coagulopathy Workup
Start with the lab result. Work down to the diagnosis.
What is prolonged?
Extrinsic pathway only (Factor VII). aPTT is normal.
Warfarin blocks vit K-dependent factors (II, VII, IX, X). PT rises first because FVII has the shortest half-life (6h). Reverse with vit K, FFP, or PCC for active bleeding.
Liver makes all factors. Malabsorption depletes fat-soluble vitamin K.
Early liver disease or isolated FVII deficiency. FVII has the shortest half-life, so it drops first. PT rises before aPTT in early liver dysfunction.
Intrinsic pathway (Factors XII, XI, IX, VIII). PT is normal.
Hemophilia A (Factor VIII) or Hemophilia B (Factor IX). Distinguish with factor assays. Both X-linked recessive. Both have normal bleeding time (platelets work fine).
von Willebrand Disease. vWF carries Factor VIII (aPTT up) AND helps platelets stick (BT up). Most common inherited bleeding disorder overall.
aPTT up but no clinical bleeding. Two key differentials.
Factor XII deficiency. Prolonged aPTT but ZERO bleeding. The contact activation pathway doesn't matter clinically in vivo. Pure lab anomaly. Paradoxically increases thrombosis risk.
Lupus anticoagulant (antiphospholipid syndrome). Inhibitor antibody blocks the test in vitro. In vivo it CLOTS (DVT, PE, recurrent miscarriage). Classic: prolonged aPTT with thrombosis, not bleeding.
Common pathway or global coagulation failure. Both intrinsic and extrinsic affected.
DIC. Consumption of ALL factors and platelets simultaneously. Everything is off. Treat the underlying cause first (sepsis, obstetric emergency, trauma, malignancy).
Liver failure: can't synthesize any factors. Supratherapeutic warfarin: blocks ALL vit K-dependent factors (II, VII, IX, X) eventually affecting both PT and aPTT when factors II, IX, X all drop.
Factor X, V, II, or fibrinogen deficiency. Rare but high-yield: common pathway affects both PT and aPTT because both pathways converge at Factor X.
PT and aPTT both normal, but patient is bleeding. The coagulation cascade tests are NOT finding the problem.
Thrombocytopenia (ITP, TTP, HUS, drug-induced). Platelets are the problem, not the coagulation factors. Primary hemostasis is broken.
Platelet dysfunction (aspirin, Bernard-Soulier, Glanzmann thrombasthenia) OR vWD type 2/3. Run platelet aggregation studies and vWF antigen/activity.
Factor XIII deficiency. Cross-links fibrin into a stable clot. Without it, a soft clot forms but dissolves too easily. PT, aPTT, and bleeding time are ALL normal. Only the urea clot solubility test detects it.
Clinical Photos
What You See
Real findings that show up in clinical practice and at the bedside.
Medically reviewed by Kaitlyn Cocuzzo, MD and Fatima Ali, DO · Last updated July 5, 2026 at 8:17 PM ET
Bone Wizardry is an independent educational resource for visual learning in the medical sciences. It is not affiliated with, endorsed by, or sponsored by any licensing or examination board, contains no real or recalled examination questions, and does not guarantee any educational or examination outcome.
