HEM08 Coagulation Disorders Guide

MAPBig-picture map of coagulation disorders

LO 1Normal hemostasis, thrombin and the endothelium

Q1. What does secondary hemostasis add to the platelet plug?

The platelet plug (primary hemostasis) is weak; it needs protection from the shear stress of flowing blood
Secondary hemostasis builds a fibrin mesh that stabilizes the platelet aggregates
Platelets are not bystanders: they are vital for thrombin generation and keep thrombin localized to the injury
Coagulation "cross-talks" with the immune system and the vascular endothelium

Phase	What happens
1	Extrinsic and intrinsic pathways make prothrombinase (prothrombin activator, Xa)
2	Prothrombinase converts prothrombin → thrombin
3	Thrombin converts soluble fibrinogen → insoluble fibrin, the "scaffolding" of the thrombus

Coagulation cascade and fibrinolysis shown as a balance between bleeding and thrombosis — Clot formation and clot breakdown kept in balance

Analogy — sandbags and cement

The platelet plug is a wall of sandbags thrown into the breach. Fibrin is the cement poured over them so the current can't wash them away.

Q2. Why is thrombin both a clotting and an anticlotting protein?

Prothrombotic (at the injury)

Cleaves fibrinogen → fibrin
Activates XIII → cross-links fibrin
Feeds back: activates V, VIII, XI
Releases FVIII from vWF
Activates platelets

Antithrombotic (on intact endothelium)

Binds thrombomodulin → loses its clotting function
Thrombin–thrombomodulin activates protein C
APC + cofactor protein S destroy Va and VIIIa
Keeps the clot from spreading onto healthy wall

In-house exam

"Thrombin bound to thrombomodulin" = activates protein C (anticoagulant). Expect thrombin's dual role to be tested.

Step 1

Direct thrombin inhibitors: argatroban, bivalirudin, dabigatran. Heparin works indirectly, through antithrombin.

Q3. How does the endothelium block clots, and how does it promote them?

Target	Healthy endothelium (anti-clot)	Injured endothelium (pro-clot)
Platelets	PGI₂, NO, ADPase	Releases vWF, exposes collagen
Coagulation	Heparan sulfate (→ antithrombin), thrombomodulin (→ protein C), TFPI	Tissue factor
Fibrinolysis	tPA	PAI-1
Tone	Vasodilation	Endothelin

Normal endothelium with antithrombotic properties versus injured endothelium with prothrombotic properties — Intact endothelium (top) vs injured endothelium (bottom)

Memory tool

Healthy endothelium is Teflon; injured endothelium is Velcro. Inflamed endothelium (calcified plaque, autoimmune attack) can turn Velcro even without a cut.

Q4. What are the body's natural anticoagulants?

Brake	Action	Clue when missing
Antithrombin (III)	Inhibits Xa and thrombin (also IXa, XIa, XIIa)	Heparin doesn't raise the aPTT; nephrotic syndrome
Heparin	From basophils (and mast cells); potentiates antithrombin	—
Antithromboplastin (TFPI)	Inhibits tissue factor	—
Proteins C + S	Activated by thrombin; degrade Va and VIIIa	Venous clots; warfarin skin necrosis

Protein C and protein S pathway on the endothelial surface — Protein C/S pathway: thrombomodulin → APC → inactivates Va and VIIIa

High yield

Lose a procoagulant (VIII, IX, XI) → bleeding. Lose or break an anticoagulant (protein C, protein S, FV Leiden) → thrombosis.

Memory tool

Protein C Cancels, protein S Stops: together they shut off V and VIII.

ApplyLO 1 application questions

A1Thrombin binds a receptor on healthy endothelium and stops clotting. Which receptor, and what does it switch on?

Thrombomodulin; it activates protein C, which (with protein S) destroys Va and VIIIa.

A2Which endothelial product is the main clot-breaking signal?

tPA (converts plasminogen to plasmin).

LO 2The cascade, PT and aPTT

Q1. Where are the clotting factors made, and which need vitamin K?

All coagulation proteins are made exclusively in hepatocytes, except FVIII
Vitamin K–dependent: II, VII, IX, X, protein C, protein S (vitamin K lets them be γ-carboxylated)

Factor	Name	Note
I	Fibrinogen	Common pathway
II	Prothrombin	Vit K
III	Tissue factor	Extrinsic
IV	Calcium	All steps
V	Labile factor	Cofactor for Xa; FV Leiden
VII	Stable factor	Vit K; shortest half-life
VIII	Antihemophilic factor A	Not from hepatocytes; carried by vWF
IX	Christmas factor	Vit K; hemophilia B
X	Stuart-Prower	Vit K
XI · XII · XIII	Antihemophilic C · Hageman · fibrin-stabilizing	XI = hemophilia C

Liver with vitamin K producing factors II, VII, IX and X

Vitamin K–dependent factors

Made in the liver: II, VII, IX, X (+ C, S)

In-house exam

"The only coagulation protein not made in hepatocytes" = Factor VIII.

Step 1

FVIII is made by endothelial cells (liver sinusoids and elsewhere). That is why FVIII stays normal in liver disease but falls in DIC.

Memory tool

Vitamin K factors = "1972": 10, 9, 7, 2 (+ proteins C and S).

Q2. How do the extrinsic, intrinsic and common pathways run?

Pathway	How it starts	Key step
Extrinsic	"Extrinsic" to plasma: needs tissue damage; key protein = tissue factor	TF binds VIIa → TF–VIIa activates X
Intrinsic ("contact")	Factors already in blood; XII activated by kallikrein on negatively charged surfaces (platelets)	IXa + VIIIa (tenase) activates X
Common	Starts at Xa from either arm	Xa + Va (prothrombinase) → thrombin → fibrin

Clotting cascade drawing with thrombin at the center

Cascade with thrombin feedback

Green arrows: thrombin activates V, VIII, XI, XIII

Box diagram of intrinsic, extrinsic and common pathways

Three pathways

Intrinsic + extrinsic converge on Xa

Analogy — the spark and the amplifier

The extrinsic pathway is the spark (tissue factor lights the fire). The intrinsic pathway is the amplifier that turns a spark into a blaze of thrombin.

Trap

FXII deficiency → very long aPTT but no bleeding. FXIII deficiency → bleeding (umbilical stump) with normal PT and aPTT.

Q3. What do the PT and aPTT measure, and what prolongs each?

PT → extrinsic

Add thromboplastin (tissue factor) + Ca²⁺ to citrated plasma
Reported as INR to standardize between labs
Prolonged by: liver disease, DIC, vitamin K deficiency, warfarin, FVII deficiency

aPTT → intrinsic

Add kaolin + phospholipid + Ca²⁺
Prolonged by: heparin, factor deficiency (VIII, IX, XII, XI)
Nonspecific inhibitor: lupus anticoagulant
Specific inhibitor: acquired FVIII inhibitor

PT test tube: thromboplastin added to citrated plasma

PT

Add thromboplastin → VII → X/V → thrombin

aPTT

Add kaolin + phospholipid → XII, XI, IX/VIII → X/V

In-house exam

Know the three tests cold: PT → extrinsic, aPTT → intrinsic, thrombin time → common pathway (fibrinogen → fibrin).

Memory tool

"PeT" = PT, extrinsic, tissue factor. "WEPT" = Warfarin, Extrinsic, PT. "HIP" = Heparin, Intrinsic, PTT.

ApplyLO 2 application questions

A1A patient with cirrhosis has a long PT and aPTT. Which factor level would still be normal?

Factor VIII (not made in hepatocytes).

A2A newborn who skipped the vitamin K shot bleeds on day 4. Which test rises first, and why?

PT: FVII has the shortest half-life, so it falls first.

LO 3Plasmin and fibrinolysis

Q1. How does plasmin break down a clot?

Normal endothelium sits in an anticoagulant state and makes tPA
tPA converts plasminogen → plasmin; plasmin cleaves fibrin and fibrinogen
Fibrinolysis keeps the clot sized to the injury: clot formation and clot breakdown stay in balance

Step 1

Alteplase (tPA) dissolves clots. Tranexamic acid / aminocaproic acid block plasminogen activation and protect clots (used in hemophilia and vWD dental bleeding). D-dimer is a sensitive rule-out; ↑ in DVT, PE and DIC.

Analogy — the cleanup crew

Plasmin is the cleanup crew that arrives after the repair. PAI-1 and α2-antiplasmin are the foremen who stop them from tearing the patch out too soon.

ApplyLO 3 application question

A1A hemophilia patient needs a tooth pulled. Which drug class protects the clot in the mouth?

Antifibrinolytics (tranexamic acid or aminocaproic acid), with factor replacement as needed.

LO 4Working up a bleeding patient

Q1. How does the bleeding pattern point to platelets or factors?

	Platelet / vWF (primary)	Factor (secondary)
Where	Skin + mucosa: petechiae, purpura, epistaxis, gums, heavy menses	Deep: joints, muscles, soft tissue, retroperitoneum, brain
When	Immediately after a cut	Delayed, prolonged
Petechiae	Yes	No
Examples	ITP, vWD, Bernard-Soulier, Glanzmann	Hemophilia A/B, vitamin K deficiency, warfarin

High yield

Bleeding into joints → coagulation cascade problem. Bleeding into skin/mucosa → platelet problem.

Q2. Which tests do I order, and how do I read them?

Test	Checks
Platelet count	Number
Bleeding time / PFA-100	Platelet + vWF function
PT · aPTT · TT	Extrinsic · intrinsic · common (fibrinogen → fibrin)
Mixing study (1:1 normal plasma)	Corrects → factor deficiency · doesn't → inhibitor (lupus anticoagulant, acquired FVIII inhibitor, heparin)
Factor assays	Which factor, and how severe
vWF antigen · activity (ristocetin cofactor) · ristocetin aggregation	Amount and function of vWF
Fibrinogen · D-dimer	Consumption (DIC)

Trap — lupus anticoagulant

It prolongs the aPTT in the tube (binds the phospholipid) and doesn't correct on mixing, but in the body it causes clots and miscarriage (antiphospholipid syndrome).

Memory tool

Mixing study: "add the missing piece." If the patient is just missing a factor, normal plasma fills the gap and the time corrects. If something is attacking the factor, the attacker eats the new plasma too.

Q3. What is the lab pattern for each disorder?

Disorder	Plt	BT	PT	aPTT	Mixing	Tie-breaker
Hemophilia A / B / C	N	N	N	↑	Corrects	↓ VIII / IX / XI
FVII deficiency	N	N	↑	N	Corrects	Isolated PT
vWD type 1	N	↑	N	N/↑	Corrects	↓ vWF Ag + activity
vWD type 2B	↓ mild	↑	N	N/↑	—	↑ GPIb affinity
Vit K deficiency / warfarin	N	N	↑ first	↑ later	Corrects	↓ II, VII, IX, X
Heparin	N	N	N/↑	↑	Doesn't	↑ TT
Liver disease	↓	N/↑	↑	↑	Corrects	FVIII normal
DIC	↓	↑	↑	↑	—	↓ fibrinogen, ↑ D-dimer
Acquired FVIII inhibitor	N	N	N	↑	Doesn't	Older adult, new bruising
Lupus anticoagulant	N	N	N	↑	Doesn't	Clots, miscarriage
Factor V Leiden	N	N	N	N	—	APC resistance

Trap — liver vs DIC

Both prolong PT and aPTT. FVIII normal → liver disease. FVIII low + ↓ fibrinogen + ↑ D-dimer + schistocytes → DIC.

Step 1

DIC causes: SSSTOP making thrombi: heat Stroke, Snake bites, Sepsis, Trauma, Obstetric complications, acute Pancreatitis (+ malignancy, nephrotic syndrome, transfusion).

ApplyLO 4 application questions

A1A 68-year-old woman with no bleeding history has a large thigh hematoma; aPTT 78 that does not correct on mixing; FVIII 2%. Diagnosis?

Acquired hemophilia A (autoantibody against FVIII).

A2A woman has a DVT and a past miscarriage; aPTT 58, not corrected by mixing. Which antibody?

Anticardiolipin / lupus anticoagulant → antiphospholipid syndrome.

LO 5Hemophilia A and B

Q1. What causes hemophilia, and who gets it?

"Love of bleeding." Hemophilia A = defective or deficient FVIII; hemophilia B (Christmas disease) = FIX
Both X-linked recessive; clinically similar; together ≈ 1 in 5,000 male births
Account for >90% of congenital bleeding disorders (lecture); A is about 5× more common than B
Mechanism: no tenase (IXa + VIIIa) → weak thrombin burst → unstable clot. Normally vWF carries inactive FVIII; injury releases it to bind FIX
⅓ are new (spontaneous) mutations, as the Haldane hypothesis predicts → a negative family history doesn't exclude it
Women are affected rarely: carrier mother + affected father, Turner syndrome (XO), extreme lyonization (chance inactivation of most normal X's)

X-linked recessive

Carrier mom → 50% of sons affected, 50% of daughters carriers

In-house exam

Inheritance of hemophilia A and B = X-linked recessive. Hemophilia C (FXI) is autosomal: males and females equal.

Memory tool

"Hemophilia Ate" → A = eight (VIII). B = Christmas (IX: nine days of Christmas left to remember). C = Common to both sexes.

Q2. How does hemophilia present, and how does severity track factor level?

Severity	Factor level	Bleeding
Severe	<1% of normal	Spontaneous bleeding into joints (hemarthroses) and muscles
Moderate	1–5%	After trauma or surgery; occasionally spontaneous
Mild	>5–<40%	Only after trauma or surgery

Spontaneous joint bleeds, often into one target joint; soft-tissue bleeds after minor trauma
Average age of first joint bleed in severe hemophilia ≈ 18 months (when toddlers start walking)
Other clues: bleeding after circumcision or from the umbilical stump, hematuria ("pink-tinged urine"), no petechiae
Labs: ↑ aPTT, normal PT, platelets and bleeding time; mixing corrects; ↓ factor level

Hemarthrosis

Spontaneous bleeding into a target joint

Large soft-tissue bruise on a child's back

Soft-tissue bleed

Large hematoma after minor trauma

Severity by factor level

<1% severe · 1–5% moderate · 5–40% mild

High yield

Boy + hemarthroses + isolated ↑ aPTT that corrects on mixing = hemophilia. Untreated, the classic consequence is hemarthroses → joint deformity.

Trap

Hemophilia A and B are clinically identical; only a factor assay separates them. Neither causes petechiae.

Q3. How do hemophilia B and C differ from A?

	A	B (Christmas)	C
Factor	VIII	IX (vitamin K–dependent serine protease)	XI
Inheritance	X-linked recessive	X-linked recessive	Autosomal; M = F
Frequency	≈5× B	≈1:100,000 males	Rare (Ashkenazi Jewish)
Bleeding	Spontaneous joints/muscles when severe		Only with trauma; no joint/muscle bleeds
Notes	Most common hemophilia	Mostly point mutations; in 14% FIX is present but non-functional	Bleeds at surgery

Hemophilia C

Bleeding after trauma; spares joints and muscles

Q4. How is hemophilia treated, and what are the complications?

A: FVIII concentrate (prophylaxis), emicizumab, desmopressin if mild (releases stored FVIII + vWF)
B: FIX concentrate (desmopressin doesn't help)
C: FFP or antifibrinolytics around surgery
Adjuncts: tranexamic acid for mucosal/dental bleeding
Complications: arthropathy (target joint destroyed), intracranial hemorrhage, inhibitors (alloantibodies against infused factor → bypassing agents)

Step 1

Emicizumab is a bispecific antibody that bridges IXa and X, doing VIII's job, so it works even when the patient has FVIII inhibitors.

ApplyLO 5 application questions

A1A 2-month-old boy bruises when his mother touches him, has pink urine, and his umbilical stump bled for days. aPTT 100 s, PT 10 s. Mom is adopted. Diagnosis and next test?

Hemophilia A most likely (more common than B). Next: mixing study (corrects) → FVIII and FIX assays. Unknown family history fits the ⅓ new-mutation rate, too.

A2A woman's father has hemophilia A. What is the chance her son is affected?

50%. She is an obligate carrier; each son has a 50% chance, each daughter a 50% chance of being a carrier.

A3Why is acquired hemophilia unlikely in that 2-month-old?

It is rare at that age, and the bleeding has been present since birth (umbilical stump), pointing to an inherited defect.

LO 6von Willebrand disease vs hemophilia A

Q1. What does vWF do, and what goes wrong in vWD?

vWF has two jobs: (1) glue: bridges platelet GPIb to subendothelial collagen (adhesion) and helps platelet–platelet binding; (2) bodyguard: carries and protects FVIII
vWD = ↓ amount or ↓ function of vWF → poor adhesion (mucosal bleeding) ± low FVIII (mild ↑ aPTT)
Most common inherited bleeding disorder (≈1%); mostly autosomal dominant → males and females

Normal clotting where platelets stick together versus vWD where platelets don't stick

Normal vs vWD

Without vWF, platelets don't stick at the tear

Autosomal dominant

Types 1 and 2: sons and daughters equally

Analogy — the glue and the bodyguard

vWF is glue for platelets and a bodyguard for FVIII. Lose the glue → skin and mucosal bleeding. Lose the bodyguard → FVIII is cleared faster and the aPTT creeps up.

Q2. What are the vWD types?

Type	Defect	Key point
1	Partial quantitative deficiency	Most common; mild; DDAVP works
2A	Qualitative: loss of high-molecular-weight multimers	↓ platelet-dependent function
2B	Qualitative: ↑ affinity for GPIb	Clumps platelets → thrombocytopenia; ↑ aggregation to low-dose ristocetin; DDAVP worsens it → give donor vWF
2M	Qualitative: ↓ platelet-dependent function, normal multimers	—
2N	Qualitative: can't bind FVIII	Low FVIII; mimics hemophilia A
3	Complete deficiency	Severe; very low FVIII; joint bleeds like hemophilia

Table classifying von Willebrand disease types

Classification

1 = less · 2 = broken · 3 = none

Memory tool

"1 = less, 2 = broken, 3 = none." 2B = Binds platelets too well (and Bad with DDAVP). 2N = No FVIII binding.

Step 1

Type 3 is usually autosomal recessive. Acquired vWD shows up with aortic stenosis (shear destroys large multimers; Heyde syndrome with GI angiodysplasia bleeding).

Q3. How is vWD diagnosed?

PT normal, platelet count normal (mildly low in 2B), aPTT normal or ↑ (if FVIII low), bleeding time ↑
vWF antigen assay → amount of vWF protein
vWF activity (ristocetin cofactor assay) → function
Platelet aggregation testing → no aggregation to ristocetin (corrected by adding normal plasma, unlike Bernard-Soulier)

Aggregometry

vWD: flat line with ristocetin

Summary slide of von Willebrand disease: role, clinical, laboratory and treatment

vWD summary

Easy bruising, mucosal bleeding; treat with DDAVP

Trap

Normal PT, aPTT and platelets do not rule out vWD. A normal "baseline panel" in a patient with mucosal bleeding means order vWF studies.

Q4. How do I tell vWD from hemophilia A?

	vWD	Hemophilia A
Defect	↓ or abnormal vWF (→ secondary ↓ FVIII)	↓ or abnormal FVIII
Inheritance	Autosomal dominant (mostly)	X-linked recessive
Who	Males and females	Almost always males
Bleeding	Mucocutaneous: bruising, epistaxis, heavy menses, dental	Deep: joints, muscles; delayed
Bleeding time	↑	Normal
PT / aPTT	N / N or ↑	N / ↑
vWF · ristocetin	↓ · ↓	N · N
Treatment	Desmopressin, vWF concentrate, TXA, hormonal therapy for menses	FVIII; DDAVP if mild

von Willebrand disease: nosebleed and large bruise

vWD bleeding

Epistaxis and easy bruising

High yield

Normal platelet count + ↑ bleeding time + mildly ↑ aPTT + ↓ ristocetin cofactor = vWD. Classic consequence: excessive bleeding after oral surgery or tooth extraction.

Step 1

Desmopressin (DDAVP) releases vWF and FVIII stored in endothelial Weibel-Palade bodies.

ApplyLO 6 application questions

A1A 12-year-old girl's periods last 8–10 days (12+ pads/day); she had childhood nosebleeds and bruises easily; dad bled for days after wisdom teeth. PT, aPTT and platelets normal. Diagnosis and tests?

von Willebrand disease (autosomal dominant: dad affected). Order vWF antigen, vWF activity (ristocetin cofactor) and ristocetin aggregation.

A2A patient with vWD is given desmopressin and their platelet count drops sharply. Which type?

Type 2B: the abnormal vWF binds GPIb too well and clears platelets. Give donor vWF instead.

LO 7Factor V Leiden

Q1. What does normal Factor V do?

Procoagulant

Va binds Xa (prothrombinase) → speeds thrombin generation

Anticoagulant control

Activated protein C cleaves Va at specific sites → inactivates it → slows thrombin and limits clot size

FV deficiency → bleeding. Some FV mutations (FV Leiden) instead → thrombosis.

Q2. How does the Leiden mutation cause clots?

Normal sequence of events versus activated protein C resistance in Factor V Leiden

Normal vs APC resistance

Leiden Va is not cut → clot keeps growing

In-house exam

"G to A at 1691," "R506Q," "APC resistance" all = Factor V Leiden.

Memory tool

"Leiden = Lasting": Va lasts because APC can't cut it. R → Q: the APC scissors need the R.

Analogy — the stuck accelerator

Va is the gas pedal; APC lifts your foot off. In FV Leiden the pedal is jammed: the brake pulls, but the pedal won't come up.

Q3. Who has it, and what does it cause?

Group	Heterozygous frequency
General US / European	3–8% (low thrombosis risk)
Caucasian Americans	5.2%
Hispanic Americans	2.2%
Native Americans	1.25%
African Americans	1.2%
Asian Americans	0.45%
Homozygous	1:5,000 (much higher risk)

Extremely rare in Asian, African and Indigenous Australian populations
Clinical: spontaneous venous thrombosis, usually at a young age: any extremity (DVT), pulmonary vasculature, portal and mesenteric veins
Triggers stack on top: estrogen (OCPs), pregnancy, surgery
PT and aPTT are normal; diagnose with APC resistance assay → PCR

Diagram of deep vein thrombosis in the leg veins

DVT

Thrombus in deep leg veins (popliteal, femoral)

Swollen red lower leg from deep vein thrombosis

DVT clinically

Swollen, red, tender calf

Step 1 — other inherited thrombophilias

FV Leiden: most common inherited thrombophilia; DVT, cerebral vein thrombosis, recurrent pregnancy loss
Prothrombin G20210A: 3′ UTR mutation → ↑ prothrombin; 2nd most common
Protein C/S deficiency: can't inactivate Va/VIIIa; warfarin skin necrosis
Antithrombin deficiency: heparin fails to raise aPTT; can be acquired in nephrotic syndrome

High yield

Think thrombophilia: young patient with DVT/PE, unusual sites (portal, mesenteric, cerebral), recurrent clots, strong family history.

ApplyLO 7 application questions

A1A 26-year-old on OCPs has a left-leg DVT; her mother had a PE at 40. Her plasma shows APC resistance. Diagnosis and mutation?

Factor V Leiden: G→A at 1691, R506Q in factor V.

A2Warfarin is started without heparin; on day 3 painful dark skin patches appear. Underlying deficiency?

Protein C deficiency (protein C falls fast on warfarin → transient hypercoagulable state → skin necrosis).

IDImage ID

Image 1 — knee

Hemarthrosis → factor deficiency (hemophilia).

Image 2 — back

Large soft-tissue hematoma after minor trauma → hemophilia.

Image 3 — face and skin

Epistaxis + bruising → vWD (mucocutaneous).

Image 4 — pedigree

X-linked recessive → hemophilia A/B.

Image 5 — pedigree

Autosomal dominant → vWD types 1 and 2.

Image 6 — test tube

PT: thromboplastin (TF) added → extrinsic.

Image 7 — test tube

aPTT: kaolin + phospholipid → intrinsic.

Image 8 — leg

DVT → think thrombophilia (FV Leiden) in a young patient.

MCQExam-style questions

Score: 0 / 0

1A 2-month-old boy bruises whenever his mother picks him up and has pink-tinged urine. His umbilical stump took several days to stop bleeding. aPTT 100 s (21–30), PT 10 s (7–12). Most likely diagnosis?

2A 12-year-old girl has periods lasting 8–10 days, past nosebleeds and easy bruising. Her father bled repeatedly after wisdom-tooth extraction. PT, aPTT and platelets are normal. Most likely diagnosis?

3A 23-year-old woman bruises easily. Platelets 229,000; PT 12 s; PTT 38 s, corrected by a 1:1 mix. Ristocetin-induced aggregation is markedly reduced. Which is most likely in her future?

4An 11-year-old boy has easy bruising and a pharyngeal hemorrhage after a tonsil injury; several male relatives bleed. PT 13 s; PTT 52 s, corrected by mixing. Without treatment, which complication is most likely?

5A 33-year-old woman has her second DVT in 2 years and a past first-trimester miscarriage. Platelets 180,000; PT normal; aPTT 58 s; a mixing study does not correct. Which antibody is most likely?

6A 26-year-old woman on oral contraceptives develops a left-leg DVT; her mother had a PE at 40. PT and aPTT are normal. Her plasma shows resistance to activated protein C. The underlying mutation is best described as:

7Which coagulation protein is not synthesized in hepatocytes?

8Which test measures the final common step, fibrinogen → fibrin?

9On intact endothelium, thrombin binds thrombomodulin. What is the main result?

10A woman's father has hemophilia A; her husband is unaffected. What is the chance that their son will have hemophilia A?

11Warfarin is started for a DVT without heparin bridging. On day 3 painful, dark, necrotic skin patches appear on the thighs. Which deficiency is most likely?

12A 68-year-old woman with no bleeding history has a large thigh hematoma. PT normal; aPTT 78 s, not corrected by mixing; FVIII 2%. Most likely diagnosis?

13A patient with von Willebrand disease receives desmopressin before surgery, and her platelet count falls sharply. Which vWD type does she have?

!Numbers that differ between in-house and Step 1

Item	In-house	Step 1 / board review
Hemophilia C inheritance	"Autosomal"	Autosomal recessive
vWD inheritance	Autosomal dominant	Types 1 and 2 AD; type 3 usually AR
Mild hemophilia cutoff	>5–<40% factor	Some practice-question explanations use other cutoffs; go with the lecture
FVIII source	"Not hepatocytes"	Endothelial cells (incl. liver sinusoidal)
Heparin source	Basophils	Basophils and mast cells
Normal PT (lecture case)	7–12 s	≈11–15 s; ranges vary by lab, so use the one in the stem
Hemophilia frequency	A + B ≈ 1 in 5,000 males; A ≈ 5× B	A ≈ 1 in 5,000 males; B ≈ 1 in 25,000–100,000

Learning objectives

MAPBig-picture map of coagulation disorders

LO 1Normal hemostasis, thrombin and the endothelium

Prothrombotic (at the injury)

Antithrombotic (on intact endothelium)

ApplyLO 1 application questions

LO 2The cascade, PT and aPTT

Vitamin K–dependent factors

Cascade with thrombin feedback

Three pathways

PT → extrinsic

aPTT → intrinsic

PT

aPTT

ApplyLO 2 application questions

LO 3Plasmin and fibrinolysis

ApplyLO 3 application question

LO 4Working up a bleeding patient

ApplyLO 4 application questions

LO 5Hemophilia A and B

X-linked recessive

Hemarthrosis

Soft-tissue bleed

Severity by factor level

Hemophilia C

ApplyLO 5 application questions

LO 6von Willebrand disease vs hemophilia A

Normal vs vWD

Autosomal dominant

Classification

Aggregometry

vWD summary

vWD bleeding

ApplyLO 6 application questions

LO 7Factor V Leiden

Procoagulant

Anticoagulant control

Normal vs APC resistance

DVT

DVT clinically

ApplyLO 7 application questions

IDImage ID

MCQExam-style questions

!Numbers that differ between in-house and Step 1

✓Rapid review