Disorders of Hemostasis
A clinical approach to bleeding — primary vs secondary, the bleeding history, von Willebrand disease, and reading PT & aPTT with mixing studies.
Classifying a bleeding disorder
Every bleeding disorder is placed on three dichotomies at once. Together they point to the diagnosis before a single test.
Primary vs secondary
Platelets/vWF vs coagulation factors.
Quantitative vs qualitative
Too few vs not working.
Congenital vs acquired
Born with it vs developed later.
Two hemostatic systems, two patterns
The pattern of bleeding tells you which system failed — and vWF is the bridge that sits in both.
Primary hemostasis
Endothelium + platelets.
- Early onset (immediate)
- Mucocutaneous bleeding — bruising, epistaxis, gums, menorrhagia
Secondary hemostasis
Coagulation factors.
- Late onset (delayed)
- Deep-tissue bleeding — hemarthrosis, muscle hematomas
vWF bridges both: it anchors platelets (primary) and chaperones factor VIII (secondary).
Suspect, then confirm
Suspect — clinical
Bleeding Assessment Tool (BAT) + basic tests: PT, aPTT, TT.
Confirm — targeted
vWD testing · mixing studies · factor & inhibitor assays.
Local or systemic?
Isolated hematuria, epistaxis or hematemesis is usually local pathology; a bleeding disorder shows a pattern across sites.
What makes bleeding suspicious
Red-flag history
- Bleeding after birth or circumcision
- Large spontaneous bruises, easy gum bleeding
- Menorrhagia with no gynecologic cause
- Bleeding after dental work or surgery
- Family history of hemophilia / vWD
Acquired clues
- New drug (drug-induced thrombocytopenia)
- Recent viral illness or infection
- CKD, liver disease, cancer, post-partum
- Antiplatelets / anticoagulants
Anemia + neutropenia symptoms with petechiae and mucocutaneous bleeds should raise suspicion of pancytopenia.
A 14-year-old with fatigue
Hb 9.7, microcytic (MCV 69.7), high RDW — iron-deficiency anemia. She calls her periods “fine.” Delve deeper.
Her “fine” periods last 3–4 weeks and she changes a pad between every class.
Key point: many adolescents don’t know what a normal period is.
What is a normal period?
- Bleeding ≤ 7 days
- Cycles 21–45 days
- A few hours between product changes
Red flags: large clots, “gushing,” overnight changes, accidents, iron deficiency.
HMB occurs in up to 37% of adolescents. The differential includes anovulation (commonest) and coagulopathy such as vWD. She has a significant bleeding history → test further.
Lab investigation, split by system
Primary hemostasis
- Platelets → CBC, platelet function tests
- vWF → vWD testing (antigen, activity, FVIII)
Secondary hemostasis
- Coagulation factors → PT and aPTT
- Mixing studies
- Factor assays
Our patient: history fits primary hemostasis; CBC normal; low vWF antigen, low vWF activity, low factor VIII → von Willebrand disease.
The commonest inherited bleeding disorder
vWF anchors platelets and carries factor VIII — so vWD spans both hemostatic systems. It affects ~1% of people (autosomal dominant). Explore the types.
Type 1 · quantitative (partial)
Mild reduction in the amount of vWF, with a proportional drop in activity. ~80% of cases.
Type 2 · qualitative (~20%)
| 2A | ↓ platelet binding + ↓ high-MW multimers |
| 2B | Gain of function — excess platelet binding → thrombocytopenia |
| 2M | ↓ platelet binding, but normal multimers |
| 2N | ↓ binding to factor VIII (looks like hemophilia) |
Type 3 · complete deficiency
No vWF produced → severe drop in factor VIII too. Rare (~1 per million), severe bleeding.
Labs: ↓ vWF antigen, ↓ ristocetin cofactor activity, normal-or-low platelets, normal-or-high aPTT, normal-or-low FVIII. Group O runs lower. Management: desmopressin, vWF replacement, tranexamic acid, estrogen for menorrhagia.
What PT and aPTT actually measure
Both mimic clotting in a tube and time it. A prolonged time means a factor is deficient or inhibited somewhere along that pathway.
PT · prothrombin time
Extrinsic + common. Reagent = tissue factor + phospholipid + calcium. Normal ~9–15 s.
Factors: VII, then X, V, II, I.
aPTT · partial thromboplastin
Intrinsic + common. Reagent = contact activator + phospholipid, no tissue factor. Normal ~25–35 s.
Factors: XII, XI, IX, VIII, then X, V, II, I.
Read PT & aPTT together
The pattern of which clock is prolonged localises the defect to a pathway. Set each result and read the differential.
This localises the pathway; specific factor assays name the culprit.
The mixing study
A prolonged clotting time has two explanations — a missing factor, or something blocking one. Mix the patient’s plasma 1:1 with normal plasma and repeat.
Factor deficiency
The normal plasma replaces the missing factor, so the time normalises.
Inhibitor
Something in the patient’s plasma blocks the factor even after mixing — a specific inhibitor, heparin, or a lupus anticoagulant.
A partial correction can mean multiple deficiencies or an inhibitor — proceed to factor levels and inhibitor studies.
The whole approach on one page
Pattern first
Mucocutaneous = primary; deep-tissue = secondary. vWF bridges both.
Take the history
BAT + red flags; ask women about periods.
Localise with PT/aPTT
Isolated PT = VII; isolated aPTT = intrinsic; both = common pathway.
Mixing decides
Corrects = deficiency; doesn’t = inhibitor.
“The pattern of bleeding and two simple clocks will localise almost any coagulopathy.”
End of lecture.
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