Coagulation Test Interpretation & Bleeding Disorders
Read the bleeding pattern, then the PT, aPTT, and mixing study
Bleeding pattern and screening tests
Localize the defect. Mucocutaneous bleeding — epistaxis, gum bleeding, menorrhagia, petechiae, and immediate oozing after cuts — reflects a platelet or vWF problem (primary hemostasis): vWD, thrombocytopenia, or platelet dysfunction. Hemarthroses, deep muscle hematomas, and bleeding that starts hours to days after surgery reflect a coagulation factor deficiency (secondary hemostasis), classically hemophilia.
What the tests measure. The PT tests factor VII plus the common pathway (X, V, II, fibrinogen); the aPTT tests XII, XI, IX, and VIII plus the common pathway. Factor VII has the shortest half-life (about 6 hours), so warfarin, early vitamin K deficiency, and early liver disease prolong the PT before the aPTT.
| Pattern | Bleeding causes | Non-bleeding or drug causes |
|---|---|---|
| Isolated long PT | Factor VII deficiency, early vitamin K deficiency, early liver disease | Warfarin |
| Isolated long aPTT | Hemophilia A (VIII), hemophilia B (IX), factor XI deficiency (Ashkenazi Jewish ancestry; bleeding after surgery or trauma), vWD with low VIII | Unfractionated heparin; factor XII deficiency and lupus anticoagulant (no bleeding) |
| Both long | X, V, II, or fibrinogen deficiency; DIC; liver failure; severe vitamin K deficiency; massive transfusion | Warfarin excess |
| Both normal, still bleeding | Mild vWD, platelet dysfunction, factor XIII deficiency, scurvy, vascular disorders | Aspirin, NSAIDs, clopidogrel |
Bleeding with normal tests. Mild vWD is the most common explanation. Platelet dysfunction comes from aspirin, NSAIDs, clopidogrel, uremia, or inherited defects (Glanzmann thrombasthenia, Bernard–Soulier syndrome with giant platelets). Factor XIII deficiency causes delayed bleeding, umbilical stump bleeding, and poor wound healing because fibrin is never cross-linked; PT and aPTT stay normal, so order a factor XIII assay. Scurvy impairs collagen hydroxylation, producing perifollicular hemorrhages, corkscrew hairs, and swollen, bleeding gums.
Factor XII deficiency can double the aPTT yet causes no bleeding — it is no reason to cancel surgery.
Mixing studies and inhibitors
The 1:1 mix. After excluding heparin, patient plasma is mixed with an equal volume of normal plasma, immediately and after 1–2 hours at 37°C. Correction means a missing factor, since 50% activity normalizes clotting times; assay VIII, IX, XI, and XII. Persistent prolongation means an inhibitor.
Lupus anticoagulant. An antiphospholipid antibody that prolongs phospholipid-dependent tests immediately. Confirm with a dilute Russell viper venom time and phospholipid neutralization. It is an in-vitro artifact but prothrombotic in vivo, causing venous and arterial thrombosis and pregnancy loss (antiphospholipid syndrome); never give factor replacement.
Acquired hemophilia A. An autoantibody against factor VIII in older adults, postpartum women, and patients with autoimmune disease or cancer. Sudden extensive skin and muscle hematomas appear with no prior bleeding history. The aPTT is isolated, long, and fails to correct — often only after incubation — factor VIII is low, and the Bethesda assay titers the inhibitor. Treat bleeding with bypassing agents (recombinant factor VIIa or activated prothrombin complex concentrate) or recombinant porcine factor VIII (emicizumab can then prevent further bleeds), and eradicate the antibody with glucocorticoids plus cyclophosphamide or rituximab.
von Willebrand disease
Biology and diagnosis. vWF tethers platelets (via GPIb) to exposed collagen and carries factor VIII, protecting it from clearance. vWD is the most common inherited bleeding disorder, usually autosomal dominant, and presents with mucocutaneous bleeding and menorrhagia. Platelet count and PT are normal; the aPTT is normal or mildly long when VIII is low. Test vWF antigen, vWF activity (ristocetin cofactor), and factor VIII. Levels rise with pregnancy, estrogen, stress, and inflammation and run lower in blood group O, so repeat borderline results.
| Type | Defect | Treatment clue |
|---|---|---|
| 1 (~75%) | Partial quantitative deficiency | Desmopressin after a test dose |
| 2A | Loss of high-molecular-weight multimers | Often needs vWF concentrate |
| 2B | Gain of GPIb binding → platelet clearance, thrombocytopenia; enhanced aggregation at low ristocetin doses | Avoid desmopressin; vWF concentrate |
| 2N | Cannot bind factor VIII; low VIII mimics hemophilia A | vWF concentrate |
| 3 | Near-absent vWF; severe, with joint bleeds | vWF concentrate |
Treatment. Desmopressin releases vWF and VIII from endothelial Weibel–Palade bodies and is first-line for type 1; adverse effects are hyponatremia (restrict fluids), flushing, and tachyphylaxis with repeated doses. vWF-containing concentrates cover types 2 and 3, major surgery, and desmopressin nonresponders. Tranexamic acid treats mucosal bleeding (epistaxis, dental work), and hormonal therapy (combined OCPs, levonorgestrel IUD) controls menorrhagia. Avoid aspirin and NSAIDs.
Acquired von Willebrand syndrome. High shear through a stenotic aortic valve or an LVAD unfolds vWF so ADAMTS13 cleaves its largest multimers. With GI angiodysplasia bleeding, aortic stenosis gives Heyde syndrome, which improves after valve replacement. Extreme thrombocytosis and antibody-producing lymphoproliferative disorders or MGUS also cause it.
Hemophilia A and B
Genetics and presentation. Deficiency of factor VIII (hemophilia A) or IX (hemophilia B, Christmas disease) is X-linked recessive, and about a third of cases arise from new mutations; carrier females occasionally bleed. Expect hemarthroses leading to arthropathy, muscle hematomas (an iliopsoas bleed can compress the femoral nerve), delayed surgical bleeding, bleeding after circumcision, and intracranial hemorrhage. The aPTT is isolated, long, and corrects on mixing; severity follows factor activity — severe <1% with spontaneous bleeds, moderate 1–5%, mild >5–40%.
Treatment. Recombinant factor VIII or IX treats bleeds (promptly, without waiting for imaging of a painful joint) and is given as prophylaxis in severe disease. Emicizumab, a subcutaneous bispecific antibody that bridges factor IXa and X, prevents bleeding in hemophilia A with or without inhibitors; because it normalizes the aPTT regardless of true protection, aPTT-based monitoring becomes useless. Desmopressin raises factor VIII only in mild hemophilia A. Alloantibody inhibitors, mostly in severe hemophilia A, make bleeding refractory to replacement; manage with bypassing agents, emicizumab, and immune tolerance induction.
No intramuscular injections, aspirin, or NSAIDs in hemophilia — give vaccines subcutaneously and use acetaminophen for pain.
Acquired coagulopathies
Vitamin K deficiency versus liver disease. Both prolong the PT first. Vitamin K deficiency follows poor intake with broad-spectrum antibiotics, malabsorption, or warfarin, and IV vitamin K corrects the PT within about 12–24 hours. Synthetic liver failure does not respond. Factor V, which is not vitamin K–dependent, is low in liver disease but normal in vitamin K deficiency, while factor VIII, made largely by endothelium, stays normal or high in liver disease.
DIC and massive transfusion. DIC prolongs both PT and aPTT with low platelets and fibrinogen, a high D-dimer, and schistocytes; treat the cause and replace components for bleeding. Massive transfusion dilutes factors and platelets, so protocols give plasma, platelets, and red cells in roughly 1:1:1 ratios.
Uremic bleeding. Uremic toxins impair platelet adhesion (vWF–GPIb) and aggregation, leaving a normal platelet count, PT, and aPTT but a prolonged bleeding time. For active bleeding or before procedures give desmopressin, which acts within an hour but briefly; dialysis, correction of anemia, and conjugated estrogens provide longer benefit. Transfused platelets quickly become dysfunctional in uremic plasma.