Advanced Heme Exam 1

what factor in hemophilia A

VIII

what factor in hemophilia B

IX

what factor in hemophilia c

XI

lab hallmarks in hemophilia A`

increased APTT

lab hallmarks in hemophilia B

increased APTT

lab hallmarks in hemophilia C

increased APTT

lab hallmarks in factor VII deficiency

increased PT

lab hallmarks in factor V deficiency

increased PT and APTT

lab hallmarks in factor X deficiency

increased PT and APTT

lab hallmarks in factor XIII deficiency

normal PT, APTT, TT. positive clot solubility test

lab hallmarks in factor XII deficiency

increased APTT and no bleeding

lab hallmarks in fibrinogen defects

increased PT, APTT, and TT

what defect in factor 5 Leiden (APC resistance)

Arg506Gln mutation in F5 -> Factor 5 resistant to aPC

what defect in Prothrombin G20210A

increased Prothrombin (Factor II)

what defect in Protein C deficiency

decreased protein C (Vitamin K dependent)

what defect in Protein S deficiency

decreased free Protein S (Vitamin K dependent, cofactor for Protein C)

what defect in HIT (Type II)

Heparin-PF4 immune complex -> platelet activation

isolated prolonged PT points to what

factor VII deficiency or vitamin k deficiency/liver disease

isolated prolonged APTT points to what

Factor VIII, IX, and XI deficiencies (hemophilias) or inhibitor

prolonged PT and APTT points to what

common pathway factor deficiency (V, X, II, fibrinogen) or DIC

normal PT/APTT + bleeding points to what

platelet defect (qualitative) or Factor XIII deficiency

DDAVP therapy

released vWF + Factor VIII (good for mild vWD and hemophilia A)

Emicizumab therapy

bispecific Ab mimicking Factor VIII, used in hemophilia A with inhibitors

FFP therapy

broad replacement of all clotting factors

cryoprecipitate therapy

fibrinogen, vWF, Factor VIII and XIII

PCC (prothrombin complex concentrates) therapy

vitamin K-dependent factors (II, VII, IX, X)

FVII therapy

targeted rescue in severe bleeding (esp. factor VII deficiency)

what defect in Glanmann's thrombasthenia

GPIIb/IIIa deficiency -> no fibrinogen binding

lab hallmarks of GT

abnormal aggregation to ADP/epi/collagen/thrombin but normal ristocetin

what to confirm diagnosis of GT

flow cytometry (decreased CD41/61)

what defect in Bernard-Soulier Syndrom (BSS)

GPIb/IX/V deficiency -> defective adhesion

lab hallmarks in BSS

thrombocytopenia, giant PLTs, abnormal ristocetin

what to confirm diagnosis of BSS

flow cytometry (CD42b)

what defect in storage pool disorders

absent granules

lab hallmarks of storage pool disorders

normal count, defective release, variable PFA

what to confirm diagnosis of storage pool disorders

EM/flow cytometry

what defect in Drug-Induced disorders (aspirin, NSAIDS)

COX-1 inhibition -> decreased Thromboxane A2 (TXA2) a potent lipid mediator produced mainly by platelets and other cells, acting as a powerful vasoconstrictor and stimulator of platelet aggregation

lab hallmarks of drug-induced disorders

abnormal COL/epi PFA; normal PT/APTT

what to confirm drug-induced disorders

aggregation studies w/ arachidonic acid

what defect in vWD (type 2 variants)

qualitative vWF defects

lab hallmarks of vWD (type 2n variants)

abnormal ristocetin, activity/Ag ratio < 0.7

lab hallmarks in factor XII

increased APTT

what to confirm diagnosis of vWD type 2

vWF assays, multimer analysis

causes of thrombocytopenis

increased destruction, decreased production, or sequestration

pathology of ITP

Autoantibodies vs. GPIIb/IIIa, GPIb/IX

ITP acute

kids. post-viral, <20k PLTs, self-limited

ITP chronic

adults. 20-80k PLTs, relapsing

labs ITP

Isolated thrombocytopenia, ↑ MPV

ITP treatment

Steroids, IVIG, splenectomy, rituximab

TTP pathology

ADAMTS13 deficiency → ↑ UL-vWF multimers → platelet aggregation

treatment for TTP

Plasma exchange ± rituximab

HUS pathology

Shiga toxin → endothelial injury → microthrombi

triad (symptoms) of HUS

Hemolysis, renal failure, thrombocytopenia

HUS treatment

Supportive ± eculizumab (if complement-mediated)

DIC pathology/lab findings

Consumptive coagulopathy: ↑ PT/APTT, ↑ D-dimer, ↓ fibrinogen, thrombocytopenia

HEELP syndrome lab findings

Hemolysis, Elevated LFTs, Low PLTs

aplastic anemia PBS findings

Pancytopenia, hypocellular BM

aplastic anemia lab findings

↓ PLTs, Hgb, ANC (absolute neutrophil count); ↑ TPO (thrombopoetin)

Kasabach-Merritt Syndrome pathology

Vascular tumor → consumptive coagulopathy

Kasabach-Merritt Syndrome lab findings

↑ PT/APTT, ↑ D-dimer, ↓ fibrinogen

Essential Thrombocythemia (myeloproliferative) pathology

clonal megakaryocyte proliferation

Essential Thrombocythemia (myeloproliferative) lab findings

↑ PLTs, paradoxical bleeding + clotting

Essential Thrombocythemia (myeloproliferative) treatment

Hydroxyurea, ASA (if not bleeding risk)

von Willebrand Disease - Type I lab findings

Normal PLTs, ↑ bleeding time, ↑ APTT, abnormal ristocetin, ↓ vWF antigen/activity

vWD Type 1 treatment

DDAVP, cryoprecipitate, FVIII concentrates

Vitamin K Deficiency pathology

No γ-carboxylation → inactive Factors II, VII, IX, X, Protein C, S

vitamin k deficiency lab findings

↑ PT, ± ↑ APTT; normal FV

liver disease pathology

↓ synthesis of factors II, V, VII, IX, X, XI, XIII; ↓ Protein C/S, ATIII

liver disease lab findings

↑ PT/APTT/TT, ↑ FDP

Primary Fibrinolysis pathology

↑ plasminogen activation (no clot formation)

primary fibrinolysis lab findings

↑ PT/APTT, ↓ fibrinogen, ↑ FDP, normal D-dimer, normal PLTs, no schistocytes

how to differentiate between DIC and primary fibrinolysis

D-dimer ↑ in DIC, normal in primary fibrinolysis

Factor VIII Inhibitor (Acquired Hemophilia A) pathology

IgG vs. FVIII → prolonged bleeding

Factor VIII Inhibitor (Acquired Hemophilia A) lab findings

↑ APTT, no correction on mixing study

Lupus Anticoagulant (Antiphospholipid Syndrome) pathology

Autoantibody vs. phospholipid-protein complex

Lupus Anticoagulant (Antiphospholipid Syndrome) treatment

↑ PT/APTT (in vitro), but causes thrombosis in vivo

D-dimer

fibrin breakdown (DIC, clots, MI, COVID)

Antithrombin activity

natural anticoagulant (↓ in DIC, VTE)

Platelet Neutralization

confirms LA

DRVVT

best screen for lupus anticoagulant

Bethesda assay

quantifies FVIII inhibitor strength

ITP buzzwords

Isolated thrombocytopenia, young women, ↑ MPV

TTP buzzwords

ADAMTS13, neuro + fever + MAHA

HUS buzzwords

Children, diarrhea, renal failure

DIC buzzwords

↑ D-dimer, schistocytes, sepsis/pregnancy

Primary Fibrinolysis buzzwords

↑ FDP, normal D-dimer

Aplastic Anemia buzzwords

Pancytopenia, hypocellular marrow

Kasabach-Merritt buzzwords

Infant hemangioma + coagulopathy

HELLP buzzwords

Pregnancy, hemolysis, ↑ LFT, ↓ PLT

vWD buzzwords

Mucocutaneous bleeding, abnormal ristocetin

Lupus anticoagulant buzzwords

↑ APTT, thrombosis not bleeding

FVIII inhibitor buzzwords

APTT not corrected by mixing

Which test is a historical, operator-dependent screen of platelet adhesion/aggregation?

Bleeding Time (BT)

Which point-of-care test simulates high-shear primary hemostasis and is prolonged in vWD and with aspirin?

PFA-100/200 Closure Time (CT) — Collagen/Epinephrine and Collagen/ADP cartridges.

Name five common agonists used in Light Transmission Aggregometry (LTA).

ADP, collagen, epinephrine, arachidonic acid, ristocetin

What additional measurement does lumi-aggregometry provide and what does it assess?

ATP release (dense-granule secretion) — assesses storage pool/release defects.

What does Ristocetin-Induced Platelet Aggregation (RIPA) test for and in which disorders is it abnormal?

Tests vWF-GPIb interaction; increased sensitivity in type 2B vWD; absent in Bernard-Soulier syndrome and vWD type 3

Which platelet disorder shows giant platelets and a decreased platelet count with absent ristocetin aggregation?

Bernard-Soulier syndrome (GPIb/IX/V defect).

Which disorder has absent aggregation to most agonists (except ristocetin) and decreased CD41/CD61 on flow cytometry?

Glanzmann thrombasthenia (GPIIb/IIIa defect).

Which lab tests are first-line to evaluate quantitative platelet disorders?

CBC with platelet count & MPV, peripheral smear, IPF/reticulated platelets, bone marrow if indicated.