Master PT, aPTT, TT, and mixing studies for evaluating bleeding disorders on ASCP hematology MCQs.

ASCPprep.com | Hematology & Hemostasis

Chapter 24 โ€” HEMORRHAGIC DISORDERS AND LABORATORY ASSESSMENT

ASCP Board Exam ยท Lab-Focused Study Guide
Localized vs Generalized ยท Mucocutaneous vs Anatomic Bleeding ยท Screening Tests ยท ACOTS & Transfusion Therapy ยท Liver Disease ยท Renal Failure ยท Vitamin K Deficiency ยท Acquired Hemophilia & Mixing Studies ยท Acquired VWD ยท von Willebrand Disease (Types 1, 2A, 2B, 2M, 2N, 3) ยท Hemophilia A ยท Bethesda Assay ยท Hemophilia B ยท Hemophilia C ยท Rare Factor Deficiencies ยท Factor XIII ยท Practice Questions

1 ยท Priority Table & Quick Foundation

Topic Priority Why It’s Tested
Mucocutaneous (primary hemostasis) vs anatomic (coagulation factor) bleeding HIGH Rodak Q2, Q11
Screening test pattern for each single-factor deficiency (Table 38-7) HIGH PT/PTT/TCT interpretation
VWD types 1, 2A, 2B, 2M, 2N, 3: lab patterns (Table 38-4), RIPA, multimers, treatment HIGH Rodak Q5, Q9
Hemophilia A: X-linked, severity by factor VIII %, carrier ratio, dosing formula HIGH Most-tested bleeding disorder
Mixing studies and Bethesda assay; low vs high responders HIGH Rodak Q8; inhibitor workup
Acquired hemophilia (autoanti-VIII, type II kinetics, incubated mix) HIGH Case recognition
Liver disease vs vitamin K deficiency โ€” factor V assay HIGH Rodak Q10
Vitamin K deficiency, Coumadin overdose, newborn hemorrhagic disease HIGH Rodak Q3, Q6
Factor XIII deficiency: normal PT/PTT/TT, poor wound healing, 5-M urea test HIGH Rodak Q7
Thrombin time and reptilase time; dysfibrinogenemia MEDIUM Rodak Q4
ACOTS and transfusion thresholds (RBC, plasma, platelets, cryo, PCC, rFVIIa, TXA) MEDIUM Rodak Q1
Hemophilia B and C (Rosenthal); rare deficiencies (Table 38-8) MEDIUM Recognition
Renal failure bleeding, nephrotic syndrome, acquired VWD LOW Associations
๐ŸŽฏ KEY POINT โ€” Where to spend your time

Focus: bleeding pattern โ†’ test choice, Table 38-7 (PT/PTT/TCT per factor), VWD classification table, hemophilia severity and dosing, mixing studies/Bethesda, factor V vs VII to separate liver disease from vitamin K deficiency, factor XIII urea test. Skim: brand names of concentrates, ACOTS epidemiology, ABO reference ranges for VWF.

Quick Foundation โ€” from zero

  • Bleeding disorders are described by where the bleeding happens and why.
  • Mucocutaneous bleeding (skin and mucous membranes: petechiae, purpura, nosebleeds, gum bleeding, heavy periods) โ†’ think primary hemostasis: platelets, VWF, vessels.
  • Anatomic (soft tissue) bleeding (joints, muscles, body cavities, CNS; often delayed) โ†’ think coagulation factor deficiency, e.g., hemophilia.
  • Acquired disorders (liver disease, vitamin K deficiency, trauma, renal failure, inhibitors) are far more common than congenital ones (VWD, hemophilia A and B).
  • Lab screen: CBC with platelets, PT, PTT, thrombin time/fibrinogen โ†’ then mixing studies and factor assays.
๐Ÿ’ก Analogy

If hemostasis is patching a tire: platelets and VWF are the patch and glue โ€” if they fail, you get a slow surface leak everywhere (mucocutaneous bleeding). Coagulation factors are the vulcanizing cure โ€” if a factor is missing, the patch goes on but never hardens, so it blows out later under pressure (delayed, deep anatomic bleeding into joints and muscles). A mixing study asks: is the tire missing glue (corrects when you add normal glue), or is something in the tire dissolving the glue (inhibitor โ€” doesn’t correct)?

๐Ÿฅ Why this matters clinically

Coumadin overdose is the single most common reason for hemorrhage-related ER visits. VWD affects about 1% of people and is often missed because VWF varies with ABO group, estrogen, stress and inflammation. Detecting a factor VIII inhibitor changes treatment completely โ€” factor VIII concentrate won’t work in high responders, and bypassing agents are needed.

Concept Plain-English Explanation
Hemorrhage Severe bleeding requiring physical intervention
Petechiae / purpura / ecchymoses <3 mm / >3 mm / >1 cm skin bleeds
Hemarthrosis Bleeding into a joint
Mixing study Patient plasma + normal plasma 1:1 โ€” corrects = deficiency; doesn’t = inhibitor
Bethesda unit Reciprocal of the dilution neutralizing 50% of factor VIII in normal plasma
VWF:RCo Ristocetin cofactor โ€” VWF activity
VWF:Ag VWF antigen โ€” quantity by immunoassay
RIPA Ristocetin-induced platelet aggregation using the patient’s platelet-rich plasma

2 ยท Core Content Tables

2.1 Patterns of Bleeding

Pattern Features Typical Cause
Localized Single site; e.g., poorly sutured surgical site Injury, infection, tumor, isolated vessel defect โ€” seldom a systemic defect
Generalized Multiple sites, spontaneous, recurrent, needs intervention/transfusion Primary or secondary hemostasis disorder
Mucocutaneous (systemic) Petechiae (<3 mm), purpura (>3 mm), ecchymoses (>1 cm), gum bleeding, epistaxis, hematemesis, menorrhagia Thrombocytopenia (<150,000/ยตL), qualitative platelet disorders, VWD, vascular (scurvy, telangiectasia)
Anatomic (soft tissue) Joints (hemarthroses), muscles, body cavities, CNS, kidney (hematuria); often delayed or recurring hours later Coagulation factor deficiencies (acquired or congenital)

Epistaxis suggests a primary hemostasis defect when recurrent, >10 minutes, both nostrils, or needing intervention. Repeated hemarthroses โ†’ permanent cartilage damage.

2.2 Generalized Bleeding Signs (Box 38-1) & Congenital Indicators (Box 38-2)

Feature Details
Generalized signs Purpura; epistaxis (recurrent/>10 min); bleeding after trauma, surgery, dental extraction; multiple cavities/joints/soft tissue; several sites at once; menorrhagia; delayed or recurrent bleeding; inappropriately brisk bleeding; unexplained bleeding; hematemesis
Congenital indicators Relatives with similar symptoms; onset in infancy/childhood; bleeding from umbilical cord or circumcision; repeated hemorrhages; hemorrhage into joints, CNS, soft tissue, peritoneum
Acquired indicators Onset after childhood, linked to disease/trauma, not in relatives
Congenital frequency <1 per 100 people; most common: VWD, hemophilia A and B, platelet function disorders. Fibrinogen, II, V, VII, X, XI, XIII deficiencies rare

2.3 Screening Tests for a Generalized Hemostatic Disorder (Rodak Table 38-1)

Test Assesses
Hemoglobin, hematocrit, reticulocyte count Anemia of chronic bleeding; marrow response
Platelet count Thrombocytopenia
PT Deficiencies of II, V, VII, X (and fibrinogen)
PTT Deficiencies of all factors except VII and XIII
Thrombin time or fibrinogen assay Hypofibrinogenemia and dysfibrinogenemia
TEG / TEM Whole blood clot onset, strength and fibrinolysis within 15 min

Screening tests have clinical significance only after history and physical establish abnormal bleeding โ€” not recommended for indiscriminate screening of healthy people (false positives).

2.4 Acute Coagulopathy of Trauma-Shock (ACOTS)

Feature Details
Burden Injury = leading cause of death ages 1โ€“45; ACOTS accounts for most fatal hemorrhage
Triggers Acute inflammation, platelet activation, tissue factor release, hypothermia, acidosis, hypoperfusion (shock); worsened by colloid and RBC dilution
Massive transfusion >3 RBC units in 1 h or 8โ€“10 units in 24 h; SBP <110, pulse >105, pH <7.25, Hct <32%, Hb <10, PT >1.5ร— (INR 1.5)
RBCs Required if Hb <6.0 g/dL; contraindicated if >10.0; 6โ€“10 by clinical judgment
Plasma FP-24 (<24 h); thawed plasma 1โ€“6 ยฐC up to 5 days (VWF, V, VIII ~60% by day 5). Give for microvascular bleeding + PT >1.5ร— or PTT >2ร— mean; dose 10โ€“15 mL/kg; target 30% factor activity; 1:1 plasma:RBC ratio in trauma protocols. Risks: TACO, TRALI, thrombosis, anaphylaxis
Platelets When count <50,000/ยตL (or higher with expected loss); never if >100,000; 50โ€“100,000 for confined bleeding (brain/eye), antiplatelet drugs, platelet disorders, bypass. Generally ineffective in ITP, TTP, HIT
Concentrates Activated PCC (FEIBA, Autoplex T) 50 U/kg q12h, โ‰ค200 U/kg/24 h (DIC risk); nonactivated 4-factor PCC (Kcentra); TXA 1 g over 10 min + 1 g over 8 h
Fibrinogen Cryoprecipitate or fibrinogen concentrate when fibrinogen <100 mg/dL; 15โ€“20 mL cryo unit = 150โ€“250 mg fibrinogen; concentrate 70 mg/kg
rFVIIa (NovoSeven) FDA 1999 for hemophilia with inhibitors; ACOTS off-label 30 ยตg/kg
Monitoring TEG/TEM; platelet count, PT, PTT back to reference; fibrinogen; factor assays (target 30%)

2.5 Liver Disease Coagulopathy

Feature Details
Bleeding types Localized (esophageal varices โ€” not a coagulopathy); mucocutaneous (thrombocytopenia + platelet dysfunction); soft tissue (factor deficiency)
Factor production Liver makes nearly all factors; vitamin Kโ€“dependent II, VII, IX, X, C, S, Z made in des-ฮณ-carboxyl forms
Earliest marker Factor VII (half-life 6 h) falls first โ†’ PT prolonged even in mild disease
Factor V Decreased in liver disease, NOT vitamin Kโ€“dependent โ†’ factor V + VII assays distinguish liver disease from vitamin K deficiency
Fibrinogen Acute phase โ†‘ early (>400 mg/dL); dysfibrinogenemia (excess sialic acid) โ†’ prolonged TT and markedly prolonged reptilase time; end-stage <100 mg/dL = liver failure
VWF, VIII, XIII Acute phase reactants โ€” unaffected or โ†‘ in mildโ€“moderate disease (VWF made by ECs/megakaryocytes)
Platelets Moderate thrombocytopenia in โ…“ (sequestration, hypersplenism, alcohol toxicity); โ†“ aggregation
DIC Chronic/compensated from โ†“ AT, protein C, protein S and release of procoagulants; acute: PT, PTT, TT โ†‘, fibrinogen <100, D-dimer โ†‘โ†‘
Treatment Vitamin K (short-lived effect); plasma (2 units typical; TACO >30 mL/kg); cryo/fibrinogen concentrate if fibrinogen <50 mg/dL; platelets, PCC, AT concentrate, rFVIIa, TXA

2.6 Hemostasis Tests in Liver Disease (Rodak Table 38-2)

Assay Interpretation
Fibrinogen >400 mg/dL early/mild; <200 mg/dL moderateโ€“severe (hypo- or dysfibrinogenemia)
Thrombin time Prolonged in dysfibrinogenemia, hypofibrinogenemia, โ†‘ FDPs, and unfractionated heparin
Reptilase time Prolonged in hypofibrinogenemia, markedly in dysfibrinogenemia; not affected by heparin (Bothrops atrox venom; cleaves fibrinopeptide A only)
PT Prolonged even in mild disease; report seconds, not INR
PTT Mildly prolonged in severe disease (DIC or des-ฮณ-carboxyl II, IX, X)
Factor V Reduced in liver disease, unaffected by vitamin K deficiency
Platelet count Mild thrombocytopenia <150,000/ยตL
Platelet aggregometry Mild suppression
D-dimer >240 ng/mL (quantitative)

2.7 Renal Failure & Nephrotic Syndrome

Feature Details
Renal failure Platelet dysfunction (guanidinosuccinic acid, phenolic compounds) โ†’ mildโ€“moderate mucocutaneous bleeding; anemia and thrombocytopenia contribute
Fibrin-deposition syndromes DIC, HUS, TTP; transplant rejection; lupus nephritis โ†’ โ†‘ D-dimer, TAT, F1.2
Tests Bleeding time too unreliable; aggregometry may predict; PT and PTT expected normal
Treatment Dialysis, EPO/RBCs; desmopressin (DDAVP) raises high-molecular-weight VWF; avoid aspirin and antiplatelet drugs
Nephrotic syndrome Loss of II, VII, IX, X, XII โ€” but also AT and protein C; in 25% the regulator loss dominates โ†’ venous thrombosis

2.8 Vitamin K Deficiency & Antagonists

Feature Details
Causes Limited stores; parenteral nutrition, fad diets; fat malabsorption (biliary obstruction/atresia, chronic diarrhea โ€” fat-soluble, needs bile salts); broad-spectrum antibiotics (minor unless poor diet)
Newborns Sterile gut + little vitamin K in breast milk โ†’ hemorrhagic disease of the newborn; prevented by routine vitamin K since 1960s; II, VII, IX, X lower in newborns (lower in prematures)
Coumadin (warfarin) Blocks vitamin K epoxide reductase and quinone reductase โ†’ PIVKAs of II, VII, IX, X, C, S, Z
Superwarfarin Brodifacoum (rodenticide) โ€” effect lasts weeks to months; repeated vitamin K + PT monitoring
Most common ER cause Coumadin overdose โ€” single most common reason for hemorrhage-related ER visits
Lab Prolonged PT ยฑ PTT; mixing study corrects; factor VII lowest first, then IX, X, II
Treatment Oral or IV vitamin K (โ‰ฅ3 h to make functional factors); severe bleeding: plasma, activated/nonactivated PCC, 4-factor PCC or rFVIIa; monitor PT/INR

2.9 Acquired Hemophilia (Autoanti-VIII)

Feature Details
Autoantibodies Against II, V, VIII, IX, XIII, VWF โ€” autoanti-VIII most common
Patients Often >60 with no underlying disease; RA, IBD, SLE, lymphoproliferative disease; 2โ€“5 months after delivery (usually resolve spontaneously)
Incidence / outcome ~1 per million/year; sudden severe soft tissue, GI, GU bleeding; fatal in โ‰ฅ20%
Screening PT, PTT, TT for sudden anatomic hemorrhage: PTT prolonged; PT and TT normal; VIII <30%
Mixing study 1:1 NP mix may correct immediately but prolongs again after 1โ€“2 h at 37 ยฐC (IgG4, time- and temperature-dependent)
Kinetics Type II (autoantibodies): nonlinear; residual VIII activity; Bethesda semiquantitative ยท Type I (alloantibodies): linear, complete inactivation; accurate titers
Management Activated PCC or rFVIIa bypass the inhibitor; low titer (<5 BU) may respond to DDAVP/VIII; immunosuppression lowers titer; plasma exchange in severe cases
Other inhibitors Anti-prothrombin in ~30% with lupus anticoagulant (bleeding, prolonged PT); V and XIII inhibitors with isoniazid; anti-IIa/V after bovine thrombin/fibrin glue; acquired X deficiency in amyloidosis (adsorption)

2.10 Acquired VWD

Feature Details
Associations Hypothyroidism, autoimmune, lymphoproliferative, myeloproliferative disorders, benign monoclonal gammopathies, Wilms tumor, angiodysplasia, congenital heart disease, pesticides, HUS
Mechanisms โ†“ production, autoantibody, adsorption to abnormal cells
Lab โ†“ VWF:RCo and VWF:Ag; PT normal; PTT may be prolonged
Treatment DDAVP or plasma-derived VIII/VWF concentrate (Humate-P, Wilate, Alphanate); cryoprecipitate no longer recommended (no viral inactivation)

2.11 VWF โ€” Molecular Biology

Feature Details
History Erik von Willebrand, 1926; ~1% of population; most prevalent congenital bleeding disorder; autosomal dominant (most)
Molecule 0.8โ€“20 million Da โ€” largest in plasma; 0.5โ€“1.0 mg/dL
Synthesis ECs (Weibel-Palade bodies) and megakaryocytes (platelet ฮฑ-granules); gene on chromosome 12 (52 exons)
Processing Monomers โ†’ dimers โ†’ multimers; propeptide (VWF antigen II) cleaved; ADAMTS-13 trims ultralarge multimers (deficient in TTP)
Domains Bind factor VIII, GP Ib/IX/V, GP IIb/IIIa, collagen
VIII protection VWF prolongs VIII half-life from minutes to 8โ€“12 h
Adhesion Largest multimers best: VWF binds collagen in high-shear vessels โ†’ platelets adhere via GP Ib/IX/V โ†’ activated platelets express GP IIb/IIIa
Pathophysiology Mucocutaneous bleeding; severe deficiency also lowers VIII (<30% โ†’ anatomic bleeding). Many people have 30โ€“50% VWF with adequate VIII

2.12 Factor VIII/VWF Nomenclature (Rodak Table 38-3)

Term Meaning
VIII/VWF Plasma combination of factor VIII and VWF
VIII Procoagulant carried on VWF; with IXa forms tenase; deficiency = hemophilia A
VWF:Ag Antigenic target for VWF immunoassay
VWF:RCo Ristocetin cofactor = VWF activity โ€” ristocetin agglutinates reagent platelets via patient VWF
VWF:CBA Collagen binding assay โ€” large multimers bind collagen III
VWF:Immunoactivity Nephelometric latex assay with anti-GP Ib-binding-site antibodies
VIII:C Factor VIII coagulant activity by clot-based assay

2.13 VWD Types โ€” Mechanisms

Type Defect Key Points
Type 1 Quantitative; autosomal dominant ~75% of VWD; all multimers and VIII proportionally reduced; mildโ€“moderate bleeding after challenge; menorrhagia
Type 2A A2 domain point mutations โ†’ โ†‘ ADAMTS-13 proteolysis 10โ€“20%; small multimers predominate; large and intermediate absent; โ†“ activity, normal/slightly โ†“ antigen
Type 2B A1 domain gain-of-function โ†’ โ†‘ affinity for GP Ib/IX/V Large multimers bind platelets spontaneously โ†’ large multimers absent, intermediate present; thrombocytopenia; โ†‘ RIPA at low ristocetin. Mimic: platelet-type (pseudo) VWD (platelet GP Ib mutation)
Type 2M โ†“ platelet receptor binding Normal multimers; discrepancy between VWF:Ag and VWF:RCo
Type 2N (Normandy) Factor VIII binding site defect ‘Autosomal hemophilia‘ โ€” low VIII, normal VWF:Ag and multimers; females affected; poor response to VIII concentrate (VIII half-life minutes); confirm molecularly
Type 3 Autosomal recessive; homozygous/compound heterozygous VWF absent; VIII <5% โ†’ mucocutaneous + anatomic bleeding

2.14 Laboratory Classification of VWD (Rodak Table 38-4)

Test Type 1 Type 2A Type 2B Type 3
VWF activity (RCo, CBA, immunoactivity) Low Low Low Very low / absent
VWF antigen Low Normal to slightly โ†“ Normal to slightly โ†“ Very low / absent
Activity : antigen ratio >0.5 <0.5 <0.5 N/A
Platelet count Normal Normal Decreased Normal
PTT Normal to slightly prolonged Normal Normal Prolonged
RIPA (1 mg/mL) Decreased Decreased Increased Absent
Factor VIII activity Mildly low Normal Normal <5%
Multimers Normal pattern Large + intermediate absent Large absent All absent

2.15 VWD Laboratory Workup & Pitfalls

Feature Details
Initial CBC (exclude thrombocytopenia), PT, PTT
Standard panel VWF:Ag, VWF:RCo, factor VIII activity
Ratio RCo/Ag <0.5 (or 0.6โ€“0.7 locally) โ†’ qualitative type 2
Low-dose RIPA Patient platelet-rich plasma; 2B agglutinates at <0.5 mg/mL (even 0.1); normal/2A only >0.5 mg/mL
Multimers SDS-PAGE; separates 2A from 2B; reference labs
No longer recommended Bleeding time and PFA-100 (2009 NHLBI)
Variables raising VWF ABO (group O lowest), estrogen (pregnancy 2ndโ€“3rd trimester, OCP, HRT, menstrual cycle), inflammation, stress, exercise, crying child, tourniquet >1 min, refrigerated specimen*
Postpartum VWF falls rapidly after delivery โ†’ postpartum hemorrhage risk
Repeat Repeat panel until conclusive; acquired vs congenital by history
RCo limitations Interlab CV ~30%, detection limit 6โ€“12% โ†’ VWF:CB (collagen III) and HemosIL immunoassay alternatives
Cutoffs Low VWF: 30โ€“50%, RCo/Ag >0.5, VIII >50% ยท VWD: <30%; population-based (not ABO-stratified) per 2009 NHLBI

*Rodak lists refrigerator storage of the specimen among factors that raise VWF activity.

2.16 VWF Reference Intervals by Blood Group (Rodak Table 38-5)

Blood Group Reference Interval
O 36โ€“157%
A 48โ€“234%
B 57โ€“241%
AB 64โ€“238%
Population-based ‘Low VWF’ <50%
Population-based VWD <30%

2.17 Therapeutic Strategies in VWD (Rodak Table 38-6)

Type Primary Approach Other Options
1 Estrogen, DDAVP, EACA or TXA Factor VIII/VWF concentrate
2A Estrogen, DDAVP, EACA or TXA Factor VIII/VWF concentrate
2B Factor VIII/VWF concentrate EACA โ€” DDAVP contraindicated (releases abnormal VWF โ†’ worse thrombocytopenia)
2N Factor VIII/VWF concentrate EACA
3 Factor VIII/VWF concentrate Platelet transfusions

Mild bleeding: RICE (rest, ice, compression, elevation). DDAVP (desmopressin, antidiuretic analogue) releases VWF from storage โ€” monitor for hyponatremia. Recombinant/affinity-purified VIII contains no VWF โ€” can’t treat VWD. Monitor concentrates with VWF:Ag.

2.18 Hemophilia A โ€” Biology & Genetics

Feature Details
Frequency Hemophilias ~1 in 10,000; 85% VIII, 14% IX, 1% XI or others; second to VWD
Factor VIII 285,000 Da two-chain protein; gene on X chromosome (186 kb); thrombin releases the B domain โ†’ VIIIa detaches from VWF; VIIIa:IXa activates X 10,000ร— faster than IXa alone; labile โ€” loses ~5%/h at room temperature
Mutations Deletions, stop codons, nonsense, missense; most quantitative; rare cross-reacting material positive (normal antigen, low activity)
Inheritance Male hemizygotes bleed; female carriers usually don’t. Carrier ร— normal man: 25% normal daughter, 25% carrier daughter, 25% normal son, 25% hemophilic son. Hemophilic man ร— noncarrier: all sons normal, all daughters obligate carriers
De novo ~30% of new cases have no family history
Females with symptoms Homozygosity, double heterozygosity, extreme lyonization, new mutation on the other X; or VWD Normandy

2.19 Hemophilia A โ€” Clinical & Laboratory

Feature Details
Bleeding Deep muscle and joint (hemarthroses), hematomas, wound oozing, CNS, peritoneum, GI, kidneys; immediate or delayed hours
Neonatal Umbilical stump, circumcision, hematuria, intracranial bleeding; newborn needs โ‰ฅ2 mL unhemolyzed sample; VIII at adult levels at birth (even prematures) โ†’ factor VIII assay diagnoses it
Severity Severe <1% (spontaneous; neonatal) ยท moderate 1โ€“5% (early childhood) ยท mild 5โ€“30% (after trauma/surgery; may go undiagnosed)
Complications Musculoskeletal deformity, neurologic deficits; pre-1984 factor recipients: 70% HIV-positive or died of AIDS; hepatitis
Screening PT and TT normal, PTT prolonged (if reagent sensitive to โ‰ค30% VIII) โ†’ factor VIII, IX, XI assays
Carrier detection ~90% detected by VIII:VWF ratio below the reference limit (VWF unaffected, normalizes for estrogen etc.); genetic testing if ratio normal

2.20 Screening Results in Congenital Single-Factor Deficiencies (Rodak Table 38-7)

Deficient Factor PT PTT TCT Reflex Test
Fibrinogen Prolonged Prolonged Prolonged Fibrinogen assay
Prothrombin (II) Prolonged Prolonged Normal II, V, VII, X assays
V Prolonged Prolonged Normal II, V, VII, X assays
VII Prolonged Normal Normal VII assay
VIII Normal Prolonged Normal VIII, IX, XI assays
IX Normal Prolonged Normal VIII, IX, XI assays
X Prolonged Prolonged Normal II, V, VII, X assays
XI Normal Prolonged Normal VIII, IX, XI assays
XIII Normal Normal Normal Factor XIII quantitative assay

Contact factors (XII, HMWK, pre-K) prolong the PTT but cause no bleeding โ€” not in the table.

2.21 Hemophilia A โ€” Treatment & Dosing

Feature Details
Goal Raise VIII to hemostatic level at bleeding or before procedures; rarely >75%; twice-daily infusions (half-life 8โ€“12 h)
Prophylaxis Steady dosing keeps activity at hemostatic levels โ€” prevents long-term damage
DDAVP Raises VIII in many patients (mild hemophilia), ยฑ EACA or TXA
Concentrates Recombinant or monoclonal-purified plasma-derived; plasma-derived Alphanate, Humate-P, Wilate contain VWF + fibrinogen; since 1985 no enveloped virus transmission; nonlipid viruses (parvovirus B19, hepatitis A) possible; human-protein-free products (Bioclate)
Unit definition 1 unit = VIII activity in 1 mL normal plasma (100%)
Plasma volume Weight (kg) ร— 65 mL/kg ร— (1 โˆ’ Hct)
Dose Plasma volume ร— (target VIII โˆ’ initial VIII); repeat every 8โ€“12 h at half the first dose; also used for VWD
๐Ÿงฎ Worked Dosing Example*

70-kg man, Hct 0.40, VIII 2%, target 50%: plasma volume = 70 ร— 65 ร— 0.60 = 2730 mL. Increase needed = 0.50 โˆ’ 0.02 = 0.48. Dose = 2730 ร— 0.48 โ‰ˆ 1310 units of factor VIII. Second dose โ‰ˆ 655 units 8โ€“12 h later. *Illustrative numbers โ€” not from Rodak.

2.22 Factor VIII Inhibitors & Bethesda Assay

Feature Details
Frequency Alloantibodies in 30% of severe and 3% of moderate hemophilia A (20โ€“25% overall)
Nature Mostly IgG4, non-complement-fixing, warm-reacting; can’t be predicted
Suspect when Bleeding persists or VIII fails to rise after concentrate
Step 1 Factor VIII assay โ€” if >30%, no inhibitor
Step 2 โ€” mixing 1:1 patient + NP, incubate 1โ€“2 h at 37 ยฐC; no inhibitor โ†’ PTT within 10% of incubated NP; inhibitor โ†’ uncorrected (still prolonged)
Step 3 โ€” Bethesda Serial dilutions of patient plasma mixed with NP; VIII assayed; 1 BU = reciprocal of dilution neutralizing 50% of NP factor VIII
Low responders โ‰ค5 BU; titers don’t rise after VIII โ†’ higher VIII doses
High responders >5 BU and rise with therapy โ†’ activated PCC (FEIBA, Autoplex T) โ‰ค200 U/kg/day or rFVIIa (NovoSeven) + immunomodulation

2.23 Hemophilia B (Christmas Disease)

Feature Details
Frequency ~14% of U.S. hemophilia (โ‰ˆ hemophilia A in India)
Defect Factor IX (vitamin Kโ€“dependent serine protease; activated by XIa and VIIa)
Inheritance X-linked; heterogeneous mutations; carrier detection harder (no normalizing molecule; DNA if mutation known)
Clinical Indistinguishable from hemophilia A
Lab PTT prolonged, PT normal; do IX assay even if PTT normal (reagent insensitive to mild IX deficiency)
Treatment Recombinant or purified IX; initial dose doubled (extravascular distribution); repeat every 24 h at half dose
Inhibitors Only 3%; Bethesda; activated PCC or rFVIIa

2.24 Hemophilia C (Rosenthal Syndrome, Factor XI)

Feature Details
Inheritance Autosomal dominant* (Rodak); >half in Ashkenazi Jews
Bleeding Mildโ€“moderate; severity doesn’t correlate with XI level
Lab PTT prolonged, PT normal
Treatment Plasma infusions at hemostatic challenge

*Most references describe factor XI deficiency as autosomal (recessive with heterozygotes mildly affected); Rodak states autosomal dominant.

2.25 Rare Congenital Single-Factor Deficiencies (Rodak Table 38-8)

Deficiency Factor Level Symptoms Therapy
Afibrinogenemia No measurable fibrinogen Severe anatomic bleeding Cryo or fibrinogen concentrate to >100 mg/dL
Hypofibrinogenemia Fibrinogen <100 mg/dL Moderate systemic bleeding Same
Dysfibrinogenemia Fibrinogen activity <100 mg/dL Mild systemic bleeding Same
Prothrombin II <30% Mild systemic PCC or plasma to 75%
Factor V V <30% Mild systemic Plasma to 75%
Factor VII VII <30% Moderateโ€“severe anatomic NovoSeven, PCC, 4-factor PCC, plasma
Factor X X <30% Severe anatomic PCC or plasma to 75%
Factor XI XI <50% Anatomic Plasma to 75%
Factor XIII XIII <1% Moderateโ€“severe systemic, poor wound healing Plasma or cryo every 3 weeks

2.26 Rare Deficiencies โ€” Details

Feature Details
General Autosomal recessive, often consanguinity; dysproteinemias (activity:antigen <0.7) bleed more but fewer inhibitors; fibrinogen by Clauss assay
Factor V Platelets carry ~20% of V โ†’ prolonged bleeding time, normal aggregation; platelet concentrate is therapy; combined V + VIII deficiency (chromosome 18, Golgi transport protein)
Factor VII Bleeding doesn’t reflect level; half-life ~6 h; NovoSeven 30 ยตg/mL or 4-factor PCC โ†’ 10โ€“30%; PT (not PTT) prolonged
Factor X Half-life 24โ€“40 h; acquired in amyloidosis, paraproteinemia, antifungal therapy; PT + PTT prolonged; Russell viper venom time prolonged in X, V, II, fibrinogen deficiency but not VII
Fibrinolytic regulators Congenital ฮฑโ‚‚-antiplasmin and PAI-1 deficiencies โ†’ moderateโ€“severe bleeding (chromogenic assays)

2.27 Factor XIII Deficiency (Rodak Table 38-9)

Type Incidence XIII Activity ฮฒ-Protein ฮฑ-Protein
I Rare Absent Absent Absent
II Frequent Absent Normal Low
III Rare Low Absent Low

Plasma XIII = tetramer (2ฮฑ + 2ฮฒ); intracellular = ฮฑโ‚‚ homodimer (platelets, monocytes, placenta, prostate, uterus). ฮฑ = active enzyme site; ฮฒ = carrier/stabilizer. Normal PT, PTT, TT; weak non-cross-linked clots dissolve within 2 h in 5-M urea; confirm with chromogenic assay (Berichrom FXIII).

3 ยท Visual Memory Hooks

๐Ÿง  Bleeding pattern
โ€œSkin and Surfaces = Stickiness problem (platelets/VWF); Joints and Deep = Dough problem (factors)โ€.
๐Ÿง  Bruise sizes
โ€œPetechiae Pinpoint <3 mm, Purpura Plus >3, Ecchymosis Extra >1 cmโ€.
๐Ÿง  PTT blind spots
โ€œPTT misses 7 and 13โ€.
๐Ÿง  Normal everything but bleeds
โ€œXIII is the 13th guest nobody tests โ€” urea dissolves the clotโ€.
๐Ÿง  Liver vs vitamin K
โ€œV is Very liverโ€ โ€” V โ†“ in liver disease, normal in vitamin K deficiency.
๐Ÿง  Vitamin K deficiency
โ€œMix Corrects = Missing factors; No correction = iNhibitorโ€.
๐Ÿง  Acquired hemophilia
โ€œAutoanti-VIII is a slow burner โ€” prolongs after 1โ€“2 h incubationโ€.
๐Ÿง  Bethesda
โ€œOne BU = kills halfโ€ (50% neutralization).
๐Ÿง  Responders
โ€œLow โ‰ค5 โ†’ more VIII; High >5 โ†’ Bypass (FEIBA, NovoSeven)โ€.
๐Ÿง  Hemophilia severity
โ€œ<1 Severe, 1โ€“5 Moderate, 5โ€“30 Mildโ€.
๐Ÿง  Hemophilia inheritance
โ€œDad’s daughters are Definitely carriers; Dad’s sons are Definitely safeโ€.
๐Ÿง  Dosing
โ€œWeight ร— 65 ร— (1 โˆ’ Hct) ร— (target โˆ’ now)โ€.
๐Ÿง  IX dosing
โ€œNine needs Double the first dose, every 24โ€.
๐Ÿง  VWD types
โ€œ1 = less of normal; 2 = broken; 3 = noneโ€.
๐Ÿง  2A vs 2B
โ€œ2A = Absent large + intermediate; 2B = Big ones Bound to platelets (low platelets, โ†‘ RIPA)โ€.
๐Ÿง  2B treatment
โ€œNo DDAVP for 2B โ€” it Brings Bad VWFโ€.
๐Ÿง  2N
โ€œNormandy = Not binding VIII โ€” hemophilia in girlsโ€.
๐Ÿง  VWF and ABO
โ€œO has the Lowest VWFโ€.
๐Ÿง  DDAVP side effect
โ€œDesmopressin Drops sodiumโ€ (hyponatremia).
๐Ÿง  Recombinant VIII
โ€œRecombinant VIII has no VWF โ€” useless for VWDโ€.
๐Ÿง  Hemophilia C
โ€œC = Chosen people (Ashkenazi), level doesn’t predict bleedingโ€.
๐Ÿง  Reptilase
โ€œReptiles ignore heparinโ€.

Pattern Triggers

If you seeโ€ฆ Thinkโ€ฆ Becauseโ€ฆ
‘Bleeder’s disease’, hemarthroses, jaundice, hepatosplenomegaly, platelets 74,400, PT 18, PTT 43 Hemophilia A complicated by chronic liver disease (transfusion hepatitis) Rodak case study*
Boy with hemarthroses, PTT prolonged, PT normal Hemophilia A or B โ†’ VIII/IX assays
Woman with menorrhagia, epistaxis, family history, normal platelets VWD
Elderly patient, sudden large bruises/muscle bleeds, isolated long PTT, no history Acquired hemophilia (autoanti-VIII)
Woman 3 months postpartum with sudden soft tissue bleeding, long PTT Postpartum acquired hemophilia
Prolonged PT, corrects on mixing, patient on antibiotics/TPN Vitamin K deficiency
Prolonged PT, low V and VII Liver disease V not vitamin Kโ€“dependent
Prolonged PT, low VII, normal V Vitamin K deficiency or warfarin
Normal PT, PTT, TT; umbilical/delayed bleeding; poor wound healing Factor XIII deficiency Urea solubility
Prolonged TT, normal reptilase Heparin contamination
Prolonged TT and markedly prolonged reptilase Dysfibrinogenemia (liver disease)
VWD with low platelets, โ†‘ RIPA at low ristocetin Type 2B (or platelet-type VWD)
RCo/Ag <0.5, normal platelets, large + intermediate multimers absent Type 2A
Female with ‘hemophilia’, normal VWF:Ag, poor VIII response Type 2N
No VWF, VIII <5%, joint bleeds Type 3 VWD
Hemophiliac bleeding despite VIII, 40 BU inhibitor High responder โ†’ rFVIIa or activated PCC
Uremic patient with mucocutaneous bleeding, normal PT/PTT Renal platelet dysfunction โ†’ dialysis, DDAVP
Nephrotic syndrome with DVT Urinary loss of AT and protein C

*My interpretation โ€” the answer key isn’t in the upload.

Commonly Confused Pairs

Feature A B
Mucocutaneous vs anatomic Platelets, VWF, vessels Coagulation factors
Liver disease vs vitamin K deficiency V โ†“, VII โ†“ V normal, VII โ†“
Deficiency vs inhibitor on mixing Corrects Doesn’t correct (after incubation for VIII inhibitors)
Alloantibody vs autoantibody (VIII) Hemophiliac; type I linear kinetics; accurate titer Nonhemophiliac; type II nonlinear; semiquantitative
Low vs high responder โ‰ค5 BU; more VIII >5 BU; bypassing agents
Hemophilia A vs B VIII; 85%; carrier ratio detects 90%; q8โ€“12 h IX; 14%; double initial dose; q24 h
Hemophilia A vs VWD 2N X-linked, males; VWF normal; responds to VIII Autosomal, both sexes; poor VIII response
VWD 2A vs 2B Normal platelets, โ†“ RIPA, large + intermediate absent โ†“ platelets, โ†‘ RIPA, large absent
VWD 2B vs platelet-type VWD VWF defect Platelet GP Ib defect โ€” clinically identical
VWD 1 vs 2M Ratio >0.5 Ag/RCo discrepancy, normal multimers
Thrombin time vs reptilase time Prolonged by heparin Not affected by heparin
Plasma vs cryoprecipitate All factors; TACO risk Fibrinogen, VIII, VWF, XIII; smaller volume
Activated vs nonactivated PCC FEIBA โ€” DIC risk Kcentra โ€” safer

Timeline Table

Event Timing Key Point Best Exam Use
Factor VII fall (liver disease/warfarin) Hours (half-life 6 h) PT prolongs first Rodak Q3
Functional factors after vitamin K โ‰ฅ3 hours Severe bleeding needs plasma/PCC Rodak Q6
Mixing study incubation 1โ€“2 h at 37 ยฐC Unmasks VIII inhibitors Inhibitor detection
Postpartum acquired hemophilia 2โ€“5 months after delivery Usually resolves Recognition
VIII replacement Every 8โ€“12 h Half-life Dosing
IX replacement Every 24 h Half-life Dosing
XIII replacement Every 3 weeks Long half-life Therapy
Thawed plasma Up to 5 days at 1โ€“6 ยฐC VWF, V, VIII ~60% Blood bank
Urea clot test Dissolves within 2 h XIII deficiency Screening
Severe hemophilia diagnosis First year Neonatal bleeding Clinical

4 ยท Diagnostic Flowcharts

Flowchart 1 โ€” Approach to a bleeding patient

History and exam โ†’ Localized vs generalized; mucocutaneous vs anatomic; acquired vs congenital
Screen โ†’ CBC with platelets, PT, PTT, thrombin time or fibrinogen
Mucocutaneous + normal platelets + normal PT โ†’ VWD panel (VWF:Ag, VWF:RCo, VIII), platelet function
Anatomic + abnormal PT/PTT โ†’ Mixing study โ†’ factor assays or inhibitor workup
All normal but anatomic bleeding/poor healing โ†’ Factor XIII assay (urea solubility, chromogenic)
โš ๏ธ Common mistake: ordering screening coagulation tests on healthy people without a bleeding history โ€” false positives.

Flowchart 2 โ€” Interpreting PT, PTT, TCT (Table 38-7)

PT โ†‘, PTT normal โ†’ Factor VII
PT normal, PTT โ†‘ โ†’ VIII, IX, XI (bleeding) or XII/HMWK/pre-K (no bleeding)
PT โ†‘, PTT โ†‘, TCT normal โ†’ II, V, X โ†’ II, V, VII, X assays
PT โ†‘, PTT โ†‘, TCT โ†‘ โ†’ Fibrinogen โ†’ fibrinogen assay (ยฑ reptilase)
All normal โ†’ XIII (or platelet/vascular disorder)
โš ๏ธ Common mistake: forgetting that TCT is prolonged by heparin โ€” check reptilase time.

Flowchart 3 โ€” Mixing study and inhibitor workup

Isolated prolonged PTT โ†’ Factor VIII assay: >30% โ†’ no VIII inhibitor
VIII <30% โ†’ Mix 1:1 with normal plasma; test immediately AND after 1โ€“2 h at 37 ยฐC
Corrects and stays corrected โ†’ Factor deficiency
Corrects then prolongs after incubation โ†’ Time-dependent VIII inhibitor
Quantify โ†’ Bethesda assay โ†’ low (โ‰ค5 BU) vs high (>5 BU) responder
โš ๏ธ Common mistake: reading only the immediate mix โ€” VIII inhibitors (IgG4) need incubation.

Flowchart 4 โ€” Liver disease or vitamin K deficiency?

Prolonged PT (ยฑ PTT) โ†’ Mixing study corrects โ†’ deficiency
Factor VII and V assays โ†’ VII โ†“ + V โ†“ โ†’ liver disease
VII โ†“ + V normal โ†’ Vitamin K deficiency or warfarin
Liver disease extras โ†’ Dysfibrinogenemia (reptilase โ†‘โ†‘), thrombocytopenia, โ†‘ D-dimer; report PT in seconds, not INR
Treat โ†’ Vitamin K; plasma/PCC/cryo as needed
โš ๏ธ Common mistake: using the INR for liver disease โ€” it’s calibrated for warfarin.

Flowchart 5 โ€” Classifying VWD

Low VWF:RCo (<30%) โ†’ Check VWF:Ag and ratio
Ratio >0.5, all proportionally low โ†’ Type 1
Ratio <0.5 โ†’ Type 2 โ†’ platelet count, low-dose RIPA, multimers
โ†“ platelets, โ†‘ RIPA <0.5 mg/mL, large multimers absent โ†’ Type 2B (vs platelet-type VWD)
Normal platelets, large + intermediate absent โ†’ Type 2A ยท normal multimers โ†’ 2M
Low VIII, normal VWF โ†’ Type 2N (molecular VIII-binding assay)
VWF absent, VIII <5% โ†’ Type 3
โš ๏ธ Common mistake: diagnosing VWD from one normal result โ€” VWF fluctuates; repeat the panel.

Flowchart 6 โ€” Treating hemophilia A

Mild hemophilia or minor bleed โ†’ DDAVP ยฑ EACA/TXA
Moderateโ€“severe bleed โ†’ Factor VIII concentrate: PV ร— (target โˆ’ initial), q8โ€“12 h at half dose
VIII fails to rise / bleeding persists โ†’ Inhibitor workup
Low responder (โ‰ค5 BU) โ†’ Higher VIII doses
High responder (>5 BU) โ†’ Activated PCC (โ‰ค200 U/kg/day) or rFVIIa + immunomodulation
โš ๏ธ Common mistake: continuing standard VIII in a high responder โ€” it’s neutralized.

5 ยท 25 High-Yield Facts

# Fact
1 Mucocutaneous bleeding (petechiae, purpura, epistaxis, menorrhagia) suggests a primary hemostasis defect.
2 Anatomic soft tissue bleeding (hemarthroses, muscle hematomas) suggests a coagulation factor deficiency.
3 Acquired bleeding disorders are far more common than congenital ones.
4 The PT detects deficiencies of II, V, VII and X; the PTT detects all factors except VII and XIII.
5 Factor VII has the shortest half-life (6 h), so its deficiency affects the PT soonest.
6 Factor V is decreased in liver disease but not in vitamin K deficiency.
7 Liver disease may cause dysfibrinogenemia, prolonging the thrombin and reptilase times.
8 The reptilase time is not affected by heparin; the thrombin time is.
9 Coumadin overdose is the most common reason for hemorrhage-related emergency visits.
10 Bleeding from vitamin K deficiency is treated with vitamin K plus plasma or PCC.
11 Autoanti-VIII (acquired hemophilia) often occurs in people over 60 or 2โ€“5 months after delivery.
12 Factor VIII inhibitors are IgG4 and are time- and temperature-dependent; the mixing study must be incubated 1โ€“2 h at 37 ยฐC.
13 One Bethesda unit is the reciprocal of the dilution that neutralizes 50% of normal-plasma factor VIII.
14 High responders (>5 BU) are treated with activated PCC or rFVIIa.
15 VWD is the most common congenital bleeding disorder (~1% of the population).
16 Type 1 VWD accounts for about 75% of cases.
17 A VWF activity:antigen ratio <0.5 indicates a qualitative (type 2) VWD.
18 Type 2B VWD shows increased RIPA at low ristocetin, loss of large multimers and thrombocytopenia.
19 DDAVP is contraindicated in type 2B VWD.
20 Type 2N VWD mimics hemophilia A but affects both sexes.
21 Group O individuals have the lowest VWF levels.
22 Hemophilia A is X-linked; severe <1%, moderate 1โ€“5%, mild 5โ€“30% factor VIII.
23 Factor VIII dose = plasma volume ร— (target โˆ’ initial); plasma volume = kg ร— 65 ร— (1 โˆ’ Hct).
24 Hemophilia B (factor IX) is clinically identical to A; the initial IX dose is doubled and repeated every 24 h.
25 Factor XIII deficiency has normal PT, PTT and TT with poor wound healing; clots dissolve in 5-M urea.
โญ EXAM TIP โ€” The single most testable pattern

PT โ†‘ only = VII ยท PTT โ†‘ only = VIII, IX, XI (or contact factors, no bleeding) ยท both โ†‘ = X, V, II, fibrinogen ยท all normal with bleeding = XIII. Mix corrects = deficiency; stays prolonged (after 37 ยฐC incubation) = inhibitor โ†’ Bethesda. V separates liver disease from vitamin K deficiency. VWD: ratio <0.5 = type 2; โ†‘ RIPA + โ†“ platelets = 2B.

Quick Interpretation Table

Lab Finding Clinical Interpretation
55-year-old man: ‘bleeder’s disease’, hemarthroses, jaundice, hepatosplenomegaly, platelets 74,400, PT 18, PTT 43 Hemophilia (likely A) with chronic liver disease from transfusion-acquired hepatitis โ†’ factor VIII concentrate + treat liver coagulopathy (plasma/vitamin K)*
Anatomic bleeding, poor wound healing; PT, PTT, TT, platelets, platelet function normal Factor XIII deficiency (Rodak Q7)
Hemophilic boy bleeding with high-titer VIII inhibitor rFVIIa (Rodak Q8)
RIPA positive at <0.5 mg/mL ristocetin VWD subtype 2B (Rodak Q5)
Prolonged thrombin time Hypofibrinogenemia (Rodak Q4)
VWF:RCo 25%, VWF:Ag 28%, VIII 35%, normal platelets Type 1 VWD
VWF:RCo 40%, VWF:Ag 45%, RCo/Ag 0.9, VIII 60% ‘Low VWF’ (30โ€“50%), not VWD
PTT prolongs again after 2-h incubated mix; VIII 3%; no prior bleeding history, 68 years old Acquired hemophilia

*Case answers are my interpretation โ€” the answer key isn’t in the upload.

๐ŸŽด Flashcards โ€” Active Recall Practice

How it works: tap the card to flip it. Then mark it โœ“ Knew It or โœ— Review Again (buttons unlock after flipping). Use ๐Ÿ”€ Shuffle to randomize and ๐Ÿ Finish anytime โ€” your summary appears at the end, and you can drill only the cards you missed.

๐Ÿ“ Practice Quiz โ€” Test Your Knowledge

How it works: tap an answer for each case. You’ll get instant feedback with the full explanation and the examiner’s trap. Your final score appears once all 10 are answered.

๐Ÿชค Trap Questions โ€” Beat the Examiner

Harder on purpose. Each question targets a real misconception. After answering you’ll see the correct reasoning, the trap explained, why the examiner wrote it, and the wrong answer most students choose.

8 ยท Rapid Revision Sheet

๐Ÿ“– READ THIS 2 HOURS BEFORE YOUR EXAM

Bleeding Patterns

  • Mucocutaneous: platelets, VWF, vessels
  • Anatomic: factors (joints, muscles)
  • Petechiae <3 mm ยท purpura >3 ยท ecchymoses >1 cm
  • Congenital: infancy, cord/circumcision, family
  • Screen: CBC, PT, PTT, TT/fibrinogen

Screening Patterns

  • PT only: VII
  • PTT only: VIII, IX, XI (XII/HMWK/PK no bleed)
  • PT + PTT: X, V, II
  • PT + PTT + TT: fibrinogen
  • All normal: XIII (urea 5 M, 2 h)

ACOTS & Transfusion

  • RBC if Hb <6; none if >10
  • Plasma 10โ€“15 mL/kg; PT >1.5ร— or PTT >2ร—
  • Platelets <50,000; never >100,000
  • Cryo if fibrinogen <100 (150โ€“250 mg/unit)
  • PCC, TXA, rFVIIa; TACO/TRALI risk

Liver & Kidney

  • VII first (PT โ†‘); report seconds
  • V โ†“ in liver, normal in vitamin K deficiency
  • Dysfibrinogenemia: TT โ†‘, reptilase โ†‘โ†‘
  • Renal: platelet dysfunction โ†’ DDAVP, dialysis
  • Nephrotic: loses AT, protein C โ†’ thrombosis

Vitamin K

  • TPN, malabsorption, antibiotics, newborn
  • Coumadin overdose = #1 ER bleed
  • Brodifacoum lasts weeksโ€“months
  • Mix corrects ยท VII lowest first
  • Vitamin K (โ‰ฅ3 h) + plasma/PCC/rFVIIa

Inhibitors

  • Autoanti-VIII: >60 y or 2โ€“5 mo postpartum
  • IgG4 โ€” incubate mix 1โ€“2 h at 37 ยฐC
  • Type I (allo) vs type II (auto) kinetics
  • 1 BU = 50% VIII neutralized
  • โ‰ค5 BU more VIII ยท >5 BU FEIBA/rFVIIa

VWD Basics

  • ~1%; mostly AD; chromosome 12
  • Type 1 75% ยท 2A 10โ€“20%
  • Panel: VWF:Ag, VWF:RCo, VIII
  • Ratio <0.5 = type 2
  • O lowest; estrogen, stress, inflammation raise

VWD Subtypes

  • 2A: large + intermediate absent, โ†“ RIPA
  • 2B: large absent, โ†‘ RIPA <0.5 mg/mL, โ†“ plts
  • 2M: normal multimers, Ag/RCo discrepancy
  • 2N: VIII binding defect, both sexes
  • 3: none; VIII <5%; AR

Hemophilia A

  • X-linked; 85% of hemophilia; 30% de novo
  • <1% severe ยท 1โ€“5% moderate ยท 5โ€“30% mild
  • PT, TT normal; PTT โ†‘
  • Carrier: VIII:VWF ratio (90%)
  • Dose: kg ร— 65 ร— (1 โˆ’ Hct) ร— ฮ”; q8โ€“12 h

B, C & Rare

  • B: IX, 14%, double dose, q24 h, 3% inhibitors
  • C: XI, Ashkenazi, level โ‰  bleeding
  • VII: PT only; NovoSeven
  • X: RVVT; amyloidosis
  • XIII: types Iโ€“III; cryo q3 weeks

9 ยท Final Memory Map

  • ๐Ÿฉน HEMORRHAGIC DISORDERS
    • Bleeding Assessment
      • Localized vs generalized ยท mucocutaneous vs anatomic
      • Acquired vs congenital ยท screening tests
    • Acquired
      • ACOTS ยท liver disease ยท renal failure/nephrotic
      • Vitamin K deficiency/warfarin
      • Acquired hemophilia ยท acquired VWD ยท DIC
    • Lab Tools
      • PT ยท PTT ยท TT ยท reptilase
      • Mixing study ยท Bethesda ยท factor assays
      • VWF panel ยท RIPA ยท multimers
    • VWD
      • Types 1, 2A, 2B, 2M, 2N, 3
      • Pitfalls (ABO, estrogen, stress)
      • DDAVP, concentrates, antifibrinolytics
    • Hemophilias
      • A (VIII) ยท B (IX) ยท C (XI)
      • Severity ยท carriers ยท dosing ยท inhibitors
    • Rare Deficiencies
      • Fibrinogen, II, V, VII, X
      • XIII (urea solubility)



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