STEPTRACKERHEMATOLOGY | PATHOLOGY | HIGH-YIELD REVIEW

Coagulation Factor Disorders

Inherited and acquired factor problems — deep, delayed bleeding with an abnormal PT or PTT.

FOCUS ON
Hemophilia A (VIII) and B (IX) are X-linked, prolong the PTT only, and cause hemarthroses. von Willebrand disease is the most common inherited bleeding disorder and has a mixed pattern (mucosal bleeding, ↑ bleeding time, ± ↑ PTT). Know the reversal agents for vitamin K deficiency, liver disease, warfarin and heparin.
DISORDER
DEFECT
LABS
CLUE · TREATMENT
Hemophilia A
X-linked recessive
Factor VIII deficiency (many new mutations)
↑ PTT; PT, platelets, bleeding time normal
Boys: hemarthroses, muscle bleeds, bleeding after circumcision · factor VIII, emicizumab, desmopressin (mild)
Hemophilia B (Christmas)
X-linked recessive
Factor IX deficiency
Same pattern as A
Factor IX concentrate
Factor XI deficiency
autosomal recessive
Factor XI ↓
↑ PTT
Ashkenazi Jewish ancestry; bleeding after surgery
Acquired factor VIII inhibitor
autoantibody
IgG against factor VIII
↑ PTT that does not correct with mixing
Older adult, postpartum, autoimmune disease; sudden large bruises
von Willebrand disease
usually autosomal dominant
↓ vWF (type 1, quantity) → poor adhesion and less stable factor VIII
↑ bleeding time, normal or ↑ PTT, normal count; ↓ ristocetin cofactor activity
Menorrhagia, nosebleeds, gum bleeding · desmopressin releases vWF; vWF concentrate
Vitamin K deficiency
acquired
↓ γ-carboxylation of II, VII, IX, X, C, S
↑ PT first, then ↑ PTT
Newborn without vitamin K shot; long antibiotics; fat malabsorption · vitamin K
Liver disease
acquired
Factor synthesis ↓ (VIII spared — made by endothelium); vitamin K activation ↓
↑ PT, ↑ PTT; often ↓ platelets (spleen)
PT not corrected by vitamin K · FFP if bleeding
Factor XIII deficiency
rare
Fibrin not cross-linked → unstable clot
PT and PTT normal; clot dissolves in urea
Umbilical stump bleeding, delayed bleeding
Anticoagulant drugs
iatrogenic
Warfarin: blocks vitamin K epoxide reductase · heparin: boosts antithrombin
Warfarin ↑ PT/INR · unfractionated heparin ↑ PTT
Reverse warfarin: vitamin K + PCC · heparin: protamine · dabigatran: idarucizumab · Xa inhibitors: andexanet

Mechanism — where each defect hits

XII → XIFactor XI deficiency
→
IX + VIIIHemophilia B / A; vWF stabilizes VIII
→
X + VVitamin K, liver
→
Thrombin → fibrinWarfarin, heparin
→
XIIICross-linking

vWF does two jobs: it glues platelets to collagen and carries factor VIII. That is why vWD can prolong both the bleeding time and the PTT.

Lab patterns

DISORDER
PT
PTT
BLEEDING TIME
Hemophilia A/B
Normal
↑
Normal
vWD
Normal
Normal or ↑
↑
Vitamin K deficiency
↑
↑ (later)
Normal
Liver disease
↑
↑
Normal or ↑
Factor XIII deficiency
Normal
Normal
Normal

How it's tested

COMMON CONFUSIONHemophilia causes deep, delayed bleeding. vWD causes mucosal, immediate bleeding — even though both can lengthen the PTT.
THE TRAPA newborn whose parents declined the vitamin K shot bleeds from the gut on day 3. The PT is prolonged first, because factor VII has the shortest half-life.
YOUR APPROACHBleeding type → PT/PTT pattern → mixing study (deficiency vs inhibitor) → inheritance and family clues.

If you see… think…

Boy with knee hemarthrosis, ↑ PTT, normal PT → hemophilia A or B
Heavy bleeding after circumcision → hemophilia
Woman with menorrhagia and nosebleeds, ↑ bleeding time → vWD — desmopressin
Newborn bleeding on day 3, no vitamin K given → vitamin K deficiency bleeding
Weeks of antibiotics, then ↑ PT → loss of gut-flora vitamin K
Older woman, new big bruises, PTT doesn't correct with mixing → acquired factor VIII inhibitor
Cirrhosis, PT not fixed by vitamin K → ↓ hepatic synthesis
Umbilical stump bleeding, normal PT and PTT → factor XIII deficiency
Bleeding on warfarin → vitamin K + PCC; on heparin → protamine