HOYADOCS
Block 5 · Heme · HEM10 · Rev 1.0 · Updated Oct 8, 2026
HEM10 · Pathology · Study Guide

Clinical Evaluation of Coagulation

Updated Oct 8, 2026 Revision 1.0 4 learning objectives 4 cases

Learning objectives

  1. LO 1Separate primary from secondary hemostasis and match each to its bleeding pattern.
  2. LO 2Know what each coagulation lab measures, its normal range, and how to read the result.
  3. LO 3Place each anticoagulant on the cascade and predict which lab it moves and how it is monitored.
  4. LO 4Work through bleeding cases: name the phase, the pathway, and the tests to order.
◆ In-house exam ★ Step 1 ▲ High yield Memory tool Analogy Trap

MAPWorking up a bleeding patient in 5 steps

1 · Historywhere · when ·family · drugs 2 · Screenplatelets, PT/INR, PTT(± fibrinogen, TT) 3 · Patternwhich test is long= which pathway 4 · Mixcorrects = deficiencyno = inhibitor 5 · Confirmfactor levels, vWF panel,Bethesda, LA, aggregation All normal + mucosalmild vWDplatelet function defectaspirin / NSAIDfactor XIIIvascular (scurvy, EDS)→ vWF Ag + activity, PFA Isolated ↑ PTThemophilia A (VIII), B (IX)XI · vWD (low VIII)heparinlupus anticoagulantXII / PK / HMWK→ mix; does he bleed? Isolated ↑ PT / INRwarfarinearly vitamin K deficiencyearly liver diseasefactor VII deficiency→ VII falls first (4–6 h) ↑ PT + ↑ PTTcommon factor (X, V, II, I)liver disease · DICsevere vit K def / warfarinDOACs, DTIssupratherapeutic heparin→ platelets, fibrinogen, VIII

LO 1Primary vs secondary hemostasis

Q1. What does each phase of hemostasis do?

Primary = platelet plug

  • Players: platelets + vWF
  • Endothelial injury → collagen exposure → adhesion (vWF bridges platelet GPIb to collagen) → activation (ADP, TXA₂) → aggregation (GPIIb/IIIa + fibrinogen)

Secondary = fibrin clot

  • Players: coagulation cascade + vWF (carries/protects FVIII)
  • Factors → thrombin → fibrinogen → fibrin mesh that reinforces the plug; XIIIa cross-links it
Platelets adhering to damaged endothelium via von Willebrand factor, then aggregating

Adhesion → aggregation

  • vWF localizes platelets to the injured surface
Platelet plug stabilized by fibrin strands

Fibrin stabilizes the plug

  • Secondary hemostasis wraps fibrin around platelets
In-house exam

vWF links platelet GPIb to subendothelial collagen. Aggregation uses GPIIb/IIIa + fibrinogen.

Analogy — the sandbag wall and the mortar

Platelets are the sandbags thrown into the breach first. Fibrin is the mortar that sets around them. "The platelet stands firm waiting for reinforcements (fibrin) to arrive."

Q2. How does the bleeding pattern tell me which phase failed?
Primary defectSecondary defect
PatternMucocutaneousDeep tissue
SignsPetechiae, easy bruising, epistaxis, gum bleeding, menorrhagia, ↑ bleeding timeJoint bleeds, intramuscular hematoma, excessive or delayed bleeding after surgery or injury
CausesToo few platelets · platelet function problem · vWDFactor deficiency (congenital or acquired) · acquired inhibitors · medications · fibrinolysis
First labsPlatelet count, vWF panelPT, PTT → mix → factor levels
Palatal petechiae

Palatal petechiae

  • Primary hemostasis defect
Petechiae on both lower legs

Leg petechiae

  • Primary: platelets low or not working
Swollen knee from hemarthrosis

Hemarthrosis

  • Secondary: factor deficiency
High yield

First question on every bleeding vignette: where is the blood? Skin and mucosa → platelets/vWF. Joints, muscles, delayed → factors. Petechiae essentially never come from a factor deficiency.

Q3. Which factors sit in which pathway?
PathwayFactorsTest
Extrinsic (tissue factor)VII (+ tissue factor)PT / INR
Intrinsic (contact)XII, XI, IX, VIII (+ prekallikrein, HMWK)PTT
CommonX, V, II, I (fibrinogen)PT and PTT
Final stepI and II (thrombin → fibrin)TT
Cross-linkingXIIINone of the above
  • Vitamin K–dependent: II, VII, IX, X, protein C, protein S
  • Every factor must be activated by cleavage (zymogen → "a")
  • The extrinsic pathway initiates; the intrinsic pathway joins to build the bulk of the clot
  • Plasmin (from plasminogen trapped in the clot, activated by tPA) digests fibrin to break the clot down
Coagulation cascade showing contact activation, tissue factor and common pathways with natural anticoagulants

The cascade

  • Contact (intrinsic) · tissue factor (extrinsic) · common
Memory tool — 2 × 5 = 10, then count down from 12

Common pathway: 2 × 5 = 10 (II, V, X) (+ I). Intrinsic: count down XII, XI, (skip X), IX, VIII. Extrinsic: the leftover VII. PTT has more letters → more factors; PT has fewer letters → fewer factors.

Memory tool — "1972"

Vitamin K factors: 10, 9, 7, 2 + proteins C and S. VII has the shortest half-life → PT rises first.

In-house exam

The intrinsic pathway is triggered by contact activation: XII binds a negatively charged surface (collagen, glass, kaolin).

ApplyLO 1 application questions

A1Which coagulation factor is measured by neither PT nor PTT?
Factor XIII (cross-links fibrin after the clot forms). The PTT also doesn't assess VII.
A2A patient has nosebleeds, heavy periods and petechiae. Which phase is broken, and which labs come first?
Primary hemostasis → platelet count, then vWF antigen and activity.

LO 2The lab toolkit

Q1. Which tests check primary hemostasis?
TestWhat it isNumbers / clues
Platelet countCBC (EDTA purple top) or citrate blue / heparin green top (if EDTA clumping suspected)150–350 ×10⁹/L (in-house)
vWF antigenHow much vWF is presentvWD: antigen or activity <30%, or 30–50% with bleeding (normal 50–200%)
vWF activityHow well it works: ristocetin cofactor, multimer analysis, FVIII activity
Platelet aggregationLight transmission aggregometry with agonists: ADP, collagen, ristocetin, epinephrine, arachidonic acid, thrombin, TXA₂Hard, slow; affected by clumping, drugs, low platelets, temperature, pH, fibrinogen
Bleeding timeIncisions on the forearm under a BP cuff; time to stop1–9 min; ↑ in low platelets, function defects, aspirin, vWD · not done today
PFA-100Closure time; modern replacement for bleeding time↑ in vWD, platelet defects, aspirin
Light transmission aggregometry: light passes through platelet-rich plasma more as platelets clump

Light transmission aggregometry

  • As platelets clump, more light passes through
Aggregation tracings for ADP, adrenaline, collagen and ristocetin

Aggregation by agonist

  • One tracing per agonist; a flat line names the defect
Bleeding time test: two incisions on the forearm under a blood pressure cuff

Bleeding time

  • Operator-dependent; obsolete
Trap — vWF levels that lie

vWF is an acute-phase reactant: pregnancy, inflammation, stress, estrogen, cancer and the menstrual cycle can mask mild vWD. Repeat if normal but suspicion is high. Blood type O has ≈25% lower vWF normally.

Step 1 — aggregation patterns
  • No ristocetin response, corrects with normal plasma → vWD
  • No ristocetin response, doesn't correct → Bernard-Soulier (GPIb)
  • Ristocetin normal, everything else absent → Glanzmann (GPIIb/IIIa)
  • Arachidonic acid absent → aspirin
Q2. Which tests check secondary hemostasis, and what are the normal ranges?
TestHow / whatNormal & key point
PTAdd thromboplastin (tissue factor + Ca²⁺ + phospholipid) → time to clot. Extrinsic + common: II, V, VII, X, low fibrinogen11–15 s
INRStandardizes PT across thromboplastin reagents (WHO reference)0.9–1.2 · warfarin goal 2–3
PTTAdd Ca²⁺ + activators (kaolin, cephalin). Intrinsic + common. Does not assess VII or XIII25–40 s · monitors UFH, DTIs
Mixing studyPatient plasma 1:1 with normal pooled plasma; clot time at 0 and after incubationCorrects → deficiency · no correction → inhibitor
FibrinogenFactor I level200–400 mg/dL; need ≥100 for hemostasis; >700 → thrombosis risk; heparin can interfere
Thrombin timeAdd thrombin to plasma → fibrinogen → fibrinVery sensitive to heparin and DTIs; ↑ with low/abnormal fibrinogen
Anti-XaFunctional level of a specific drug (UFH, LMWH, DOACs)Drug-specific!

Additional tests: PFA-100, platelet electron microscopy, factor-specific assays, inhibitor assays, lupus anticoagulant, reptilase time, factor XIII, euglobulin clot lysis time, FDPs, D-dimer, PAI-1, α2-antiplasmin, TEG.

High yield

Mixing study: normal plasma restores any missing factor to ≈50%, enough to normalize the time. An antibody in the patient's plasma attacks the normal plasma's factor too, so the time stays long. Corrects at 0 but prolongs after 1–2 h at 37°C → time-dependent anti-FVIII.

Step 1

Full INR formula: (patient PT ÷ mean normal PT)ISI, where ISI = reagent sensitivity index. Reptilase time: snake venom clots fibrinogen and isn't blocked by heparin → ↑ TT + normal reptilase = heparin.

Memory tool

"PeT plays tennis outside" (extrinsic, VII). "PTT plays table tennis inside" (intrinsic: "$12 → $11.98" = XII, XI, IX, VIII).

Q3. What should I think when the PTT is long but the patient never bleeds?
  • Lupus anticoagulant: long in the tube, clots in the body
  • Contact factors: factor XII, prekallikrein or HMWK deficiency, needed in the tube but not in vivo
  • Neither needs plasma before surgery; the PTT alone isn't definitive: read it with the whole clinical picture
Memory tool

Long PTT, no bleeding = "LAX": Lupus Anticoagulant, factor XII (and its contact buddies PK, HMWK).

Trap — factor XIII

Bleeding with completely normal screens (umbilical stump, delayed bleeding, poor wound healing) → think mild vWD, platelet function, or factor XIII (clot solubility in urea).

Q4. How do I predict the full panel for each condition?
ConditionPltBT/PFAPTPTTTTFibMixKey extra
Thrombocytopenia↓↑nlnlnlnl—Smear ± marrow
Aspirin / function defectnl↑nlnlnlnl—Absent AA aggregation (aspirin)
vWDnl↑nlnl/↑nlnlCorrects↓ vWF Ag/activity, ↓ VIII
Hemophilia A / Bnlnlnl↑nlnlCorrects↓ VIII or IX
Acquired hemophilia Anlnlnl↑nlnlNo (time-dep.)↓ VIII, Bethesda
Vit K def / warfarinnlnl↑↑nl→↑nlnlCorrects↓ II, VII, IX, X; VIII nl
Liver diseasenl/↓nl/↑↑↑nl/↑nl/↓CorrectsVIII nl or ↑
DIC↓↑↑↑↑↓—↑ D-dimer, schistocytes, ↓ VIII
Lupus anticoagulantnl/↓nlnl↑nlnlNo (immediate)dRVVT; clots
XII / PK / HMWK defnlnlnl↑↑nlnlCorrectsNo bleeding
Factor XIII defnlnlnlnlnlnl—FXIII assay
Trap — liver vs DIC vs vitamin K

All prolong the PT. Factor VIII: normal/↑ in liver disease (made by endothelium), normal in vitamin K deficiency, ↓ in DIC. Vitamin K corrects only vitamin K deficiency.

In-house exam

DIC: tissue factor released into the blood → widespread thrombin → consumption of platelets, factors, fibrinogen → ↓ platelets, ↑ PT, ↑ PTT, ↓ fibrinogen, ↑ D-dimer.

ApplyLO 2 application questions

A1A 24-year-old woman has a vWF antigen of 42% and recurrent heavy periods. Does she meet in-house criteria for vWD?
Yes: 30–50% with bleeding qualifies (<30% qualifies regardless). Repeat if pregnant, inflamed or on estrogen.
A2TT is very prolonged but the reptilase time is normal. Cause?
Heparin (or a DTI) in the sample. Low fibrinogen would prolong both.
A3Why does the PT rise before the PTT in early vitamin K deficiency?
Factor VII has the shortest half-life (4–6 h) and is only measured by the PT.

LO 3Anticoagulants and the cascade

Q1. Where does each anticoagulant hit the cascade?
Anticoagulant targets: vitamin K antagonists on II, VII, IX, X; heparins and fondaparinux on Xa; heparins on thrombin; rivaroxaban, apixaban, edoxaban on Xa; dabigatran on thrombin

Drug targets

  • Two hubs: Xa and thrombin
DrugMechanismLabsMonitorReversal
Unfractionated heparinBoosts antithrombin → inactivates thrombin and Xa (long chains bridge AT to thrombin)↑ PTT, ↑ TT, ↑ anti-XaPTT (or anti-Xa)Protamine
LMWH (enoxaparin)Shortened heparin → AT acts mainly on Xa↑ anti-Xa (PTT minimal)None routinely; anti-Xa in renal failure, obesity, pregnancyProtamine (partial)
WarfarinCompetitive inhibitor of VKORC1 → depletes active vitamin K → ↓ hepatic II, VII, IX, X, C, S↑ PT / INRINR (goal 2–3)Vitamin K (slow); PCC or FFP (fast)
Rivaroxaban, apixaban, edoxabanDirect Xa inhibitors ("-xaban")PT/PTT ↑ or even normal; poor correlationNone (drug-specific anti-Xa exists, dubious use)Andexanet alfa
Dabigatran, bivalirudin, argatroban, desirudinDirect thrombin inhibitors: bind and inactivate thrombin↑ PTT, ↑ PT/INR, ↑↑ TTPTT protocol (IV DTIs)Dabigatran → idarucizumab
Memory tool

Heparin → PTT ("HePTT"). Warfarin → PT ("WePT": War is extrinsic). LMWH, fondaparinux, -xabans → anti-Xa if anything. DTIs → PTT (but every clotting test rises). "-xaban" = Xa; "-gatran" = thrombin.

Trap

The slides say heparin and LMWH "prolong the PTT and anti-Xa." True for UFH; LMWH barely moves the PTT, which is exactly why it's checked with anti-Xa when monitoring is needed.

Q2. How do UFH and LMWH differ?
  • Both enhance antithrombin's native inhibitory function
  • LMWH is made from UFH by enzymatic or chemical depolymerization into shorter chains
  • Long UFH chains bridge antithrombin to thrombin and Xa; short LMWH chains mostly reach Xa only
  • LMWH has a longer half-life and more predictable effect → no routine monitoring or titration; renally cleared
  • UFH: IV, short half-life, unpredictable → titrate by PTT
Low-molecular-weight heparin binds antithrombin to inhibit Xa; unfractionated heparin bridges antithrombin to both Xa and thrombin

LMWH vs UFH

  • Short chain: Xa · long chain: Xa + thrombin
Step 1 — HIT on one line

IgG against heparin–PF4 → platelet activation → thrombocytopenia (>50% drop, day 5–10) + thrombosis. Stop all heparin (incl. LMWH and flushes) → argatroban / bivalirudin → warfarin only after platelets recover. Fondaparinux has no HIT risk.

Q3. Why is warfarin tricky to start, and what changes its effect?
Table of half-lives after starting warfarin: protein C 8 h, protein S 30 h, factor VII 4 to 6 h, IX 24 h, X 48 to 72 h, II 60 to 72 h

Half-lives after starting warfarin

  • Protein C (8 h) and VII (4–6 h) fall first; II (60–72 h) last
  • The anticoagulant proteins (protein C) fall first → transient hypercoagulable state for a few days
  • So start heparin/LMWH first and bridge (overlap) until the INR is therapeutic (≥5 days, INR 2–3 for 24 h); full effect needs factor II to fall
  • Dose-response is highly unpredictable: drug metabolism, diet (vitamin K greens), genetics (CYP2C9, VKORC1), vitamin K–dependent factor levels, disease states, binding proteins, drug interactions, adherence
High yield

Warfarin without a heparin bridge → warfarin skin necrosis, especially with protein C deficiency.

Step 1

TMP-SMX inhibits CYP2C9 → less warfarin breakdown → ↑ INR → bleeding. Warfarin is teratogenic.

Q4. How do DOACs and DTIs affect the labs?

Direct Xa inhibitors

  • Rivaroxaban, apixaban, edoxaban
  • Drug level correlates poorly with PT or PTT; both can even be normal depending on the reagent
  • Drug-specific anti-Xa assays exist but are of dubious clinical use

Direct thrombin inhibitors

  • Dabigatran, bivalirudin, argatroban, desirudin
  • Monitored by a PTT-driven protocol
  • Also prolong PT/INR and TT → complicates bridging to warfarin in HIT
Trap

A patient with HIT started on argatroban has an INR of 3.5 before any warfarin. That's the DTI, not true warfarin effect.

ApplyLO 3 application questions

A1Which test monitors UFH? LMWH? Warfarin? Argatroban?
PTT (or anti-Xa) · usually none; anti-Xa in renal failure, obesity, pregnancy · INR · PTT.
A2Why is heparin started before, and overlapped with, warfarin?
Protein C falls first (half-life ≈8 h) → transient hypercoagulability → clots / skin necrosis. Factor II takes days to fall.

LO 4The four practice cases

Case 1. A 23-year-old man bleeding 24 hours after knee arthroscopy

Penetrating knee injury a year ago → at least 8 recurrent hemarthroses. As a child: forearm intramuscular hematoma with compartment syndrome after an injury. One of 8 siblings; 2 brothers have post-traumatic hematomas.

Swollen knee from hemarthrosis

Hemarthrosis

  • Deep, delayed bleeding → secondary
1aWhich phase of hemostasis is abnormal?
Secondary: deep, delayed, joint and muscle bleeding.
1bWhich labs?
CBC/platelets, PT, PTT → mixing study → factor VIII and IX (± XI) activity.
1cWhich pathway, and the diagnosis?
Intrinsic: ↑ PTT, normal PT, mix corrects → hemophilia A or B (X-linked, affected brothers); severity from factor level.
Case 2. A 35-year-old woman with iron deficiency anemia

Easy bruising, frequent nosebleeds, heavy periods since menarche at 13; bleeding after wisdom-tooth extraction at 18. Sister: heavy periods and easy bruising. Mother: heavy periods and postpartum hemorrhage. Maternal uncle "a bleeder."

2aWhich phase is abnormal?
Primary (mucocutaneous).
2bWhich labs?
CBC/platelets, PT, PTT, vWF antigen, vWF activity (ristocetin cofactor), multimers, factor VIII; iron studies.
2cWhich factor and pathway?
von Willebrand factor (± low VIII). Mainly primary; the PTT may be mildly ↑ (intrinsic, via VIII) → von Willebrand disease, autosomal dominant.
Trap

A "bleeder" maternal uncle tempts you toward hemophilia, but mother and sister bleeding too = autosomal dominant → vWD. Heavy periods since menarche → iron deficiency.

Case 3. A 7-day-old boy born at home with a seizure

CT: acute intracranial hemorrhage. Non-accidental trauma not suspected. Parents declined the routine erythromycin eye ointment and the vitamin K injection after delivery.

3aWhich phase is abnormal?
Secondary.
3bWhich pathway?
Extrinsic first (VII has the shortest half-life), then common and intrinsic as II, IX and X fall.
3cWhich labs, and the diagnosis?
PT/INR (↑↑), PTT (± ↑), platelets and fibrinogen (normal), factor VII (low) → vitamin K deficiency bleeding of the newborn → give vitamin K (FFP/PCC if life-threatening).
High yield

Newborns: little placental vitamin K transfer, a sterile gut (no bacterial K₂), breast milk low in K. A neonate who bleeds → think vitamin K. Prevented by IM vitamin K at birth.

Case 4. A 62-year-old woman with sudden extensive bruising

No past history. Acute, atraumatic, extensive ecchymoses on all four limbs; left thigh swelling and tenderness. No heavy periods or bleeding after wisdom teeth, tonsillectomy or cholecystectomy. No family history. CT: left quadriceps intramuscular hematoma.

4aWhich phase is abnormal?
Secondary (deep muscle bleed).
4bWhich labs?
PT (normal), PTT (↑) → mix: no correction (after incubation) → factor VIII (low) → Bethesda assay.
4cWhich pathway, and the diagnosis?
Intrinsic → acquired hemophilia A (anti-FVIII autoantibody). Treat: bypassing agents (rFVIIa, aPCC) + immunosuppression.
In-house exam

"Intramuscular hematoma + no personal or family history → mix fails → autoantibody." She survived several surgeries without bleeding, so it can't be congenital.

Memory tool — the family tells you the inheritance

Brothers / uncles → X-linked hemophilia. Mother + sister → AD vWD. Nobody + older + new → acquired inhibitor. Newborn → vitamin K.

IDImage ID

Image 1 — mouthUnknown image 1
Palatal petechiae → primary hemostasis defect.
Image 2 — legsUnknown image 2
Petechiae → low platelets or platelet dysfunction.
Image 3 — kneeUnknown image 3
Hemarthrosis → secondary (hemophilia).
Image 4 — armUnknown image 4
Bleeding time: primary hemostasis; no longer done.
Image 5 — tracingsUnknown image 5
Platelet aggregometry with a panel of agonists.
Image 6 — tableUnknown image 6
Warfarin half-lives: protein C and VII fall first → bridge with heparin.

MCQExam-style questions

Score: 0 / 0

1A 23-year-old man bleeds heavily 24 hours after knee arthroscopy. He has had 8 recurrent hemarthroses and a childhood forearm compartment syndrome; two brothers bleed after trauma. Which result is most expected?

2A 35-year-old woman has iron deficiency anemia, nosebleeds, easy bruising and heavy periods since menarche. Her mother and sister have similar bleeding. Which protein is most likely abnormal?

3A 7-day-old boy born at home has a seizure from an intracranial hemorrhage. His parents declined vitamin K at birth. Which lab is most abnormal?

4A 62-year-old woman with no prior bleeding (despite tonsillectomy and cholecystectomy) has sudden extensive bruising and a quadriceps hematoma. PT normal, PTT prolonged. Best next step?

5Which factor is not assessed by the PTT?

6Warfarin's mechanism of action is best described as:

7A patient on apixaban has a normal PT and PTT. What does this mean?

8Why does LMWH not need routine PTT monitoring, unlike unfractionated heparin?

9A patient's PTT is markedly prolonged on pre-op labs and corrects on mixing. He has never bled after dental work or surgery. Most likely?

10A cirrhotic patient has ↑ PT, ↑ PTT and platelets of 90,000. Which result best separates liver disease from DIC?

11Which fibrinogen level is the minimum needed for hemostasis?

12On day 7 of heparin, a patient's platelets fall from 250,000 to 90,000 and a new DVT appears. Best management?

!Numbers that differ between in-house and Step 1

ItemIn-houseStep 1 / board review
Platelet range150–350 ×10⁹/L150,000–400,000/mm³ (USMLE); many labs 150–450
INR formulaPatient PT ÷ control PT(Patient PT ÷ mean normal PT)ISI
Normal PT11–15 s here (7–12 s in HEM08 case; 10.7–13 s in HEM09)Varies by lab; use the range in the stem
Normal PTT25–40 s here (21–30 s HEM08; 25–38 s HEM09)≈25–40 s
Intrinsic pathway listSlides list I, II, VIII, IX, X, XI, XII (omit V)V is common pathway and still in the PTT
Heparin and LMWH"Prolong the PTT and anti-Xa"LMWH barely changes the PTT; monitored with anti-Xa
Bleeding timeTaught; normal 1–9 minObsolete; PFA-100 replaces it

✓Rapid review