Heme-coag Flashcards
Contents of platelet alpha granules
Protein molecules:
Fibrinogen
PDGF
vWF
P-selectin
PF4
Contents of platelet dense bodies
Nonprotein molecules ADP ATP serotonin (5-HT) Calcium
GPIb/XI/V complex (CD42)
mediates platelt adhesion
Receptor for vWF
GPIIb/IIIa complex (CD41&CD61)
Mediates platelet aggregation,
fibrinogen receptor
GPIaIIa
Mediates platlet adhesion
Collagen receptors
GPIc/IIa complex
Fibronectin receptor
Composition of Heinz body
Clumps precipitated hemoglobin
Hermansky-Pudlak Syndrome
-abnormal dense granules (normally secrete ADP, ATP, 5-HT and calcium) -Epistaxis, oculocutaneous albinism, pulmonary fibrosis, granulomatous colitis -ceroid-like material within tissue macrophages -common in Puerto rico
hereditary spherocytosis
AD inheritance, ANK1 (ankyrin) gene -increased MCHC, and reticulocyte count -PB: spherocytes -sx of extravascular hemolysis Abnormal osmotic fragility and autohemolysis tests (DAT is neg vs AIHA)
hereditary elliptocytosis/ovalocytosis
AD, spectrin alpha chain gene mutations -PB: elliptocytes (twice as long as wide) >25% -*hereditary pyropoikilocytosis (HPP): most common in AA, RBCs sensitive to heat *Stomatocytic type (aka southeast asian ovalocytosis): protects against P. vivax
G6PD deficiency
*G6PD needed to produce NADPH adn reduced glutathione for protection from oxidants; X-linked recessive inheritance -RBCs hypersensitive to oxidant stress (sulfa drugs, nitrofurantoin, primaquine, fava beans, infection) resulting in episodic hemolysis -p/w extravascular hemolysis -PB: bite cells*, Heniz bodies, poikilocytosis, blister cells
Pyruvate kinase (PK) deficiency
-PK catalyzes rate limiting step in glycolysis pathway
AR inheritance
-echinocytes (“burr cells”)
major adult hgb
HbA alpha2 beta2
minor adult hgb
HBA2 alpha2 delta2
Variant beta chain “S”
AA6 Glu–>Val
Variant beta chain “C”
AA6 Glu–>Lys
Relative proportion of Hgb types in sickle cell trait
SA 35-45% HbS 50-65% HbA <3% HbA2
Relative proportion of Hgb types in sickle cell disease
homozygous SS RBC lifespan of 17 days
>80% HbS 1-20% HbF 1-4% HbA2 0% HbA
screening tests for sickle cell
metabisulfite dithionate
Right shift O2 binding curve
Decreased affinity hb acidosis, increased temp, hyperthermia, increased 2,3 DPG,
Left shift O2 binding curve
Increased affinity hb alkalosis, hypothermia, decreased 2,3 DPG
What is Methemoglobin?
Hb with iron in ferric (Fe+++) state instead of usual ferrous (Fe++) state -normal low levels of Hi maintained by NADH dependent methemoglobin reductase system -treatment is methylene blue (reduces Hi to Hb)
Elevated zinc protoporphyrin
Iron deficiency anemia Anemia of chronic disease Lead poisoning
Elevated free erythrocyte protoporphyrin
Iron def anemia Anemia of chronic dx Lead poisoning
Conditions associated with arterial thrombosis
Lupus anticoagulant, HIT and hyperhomocysteinemia
What molecule is inappropriately high in anemia of chronic disease?
Hepcidin, this inhibits iron export from macrophages and enterocytes resulting in functional iron deficiency
What supports a diagnosis of anemia of chronic disease versus iron deficiency anemia
Elevated serum ferritin
Causes of intravascular hemolysis
Microangiopathic hemolytic anemia (DIC, HUS, TTP, HELLP) Complement fixation in RBC surface (ABO incompatibility, PNH, PCH) Mechanical heart valves Snake venom Infection (malaria, Vanessa, clostridium)
Heinz body composition
Insoluble hemoglobin inclusion
Pentad of TTP
Thrombocytopenia, microangiopathic hemolytic anemia, neurological abnormalities, renal dysfunction and fever
Defect in Glanzmann thrombasthenia
decreased or defective GPIIb/IIIa (fibrinogen receptor) resulting in defective platelet aggregation
ashkenazi jew with major bleeding after GU surgery
Factor XI deficiency
The following symptoms are typical of what factor deficiency: bleeding from umbilical stump, poor wound healing, hypertrophic scars.
Factor XIII deficiency Dx with urea clot lysis assay
What are the green dots? What prep? What disease
- Supravital dye
- Heinz body (denatured Hgb)
- G6PD deficiency
What 2 coagulation factors are not produced in the liver?
VIII-endothelial cells in liver
vWF-endothelial cells and megakaryocytes
which type of von willebrand disease results in profound thrombocytopenia and bleeding on exposure to DDAVP?
Type IIb
gain of function mutation in GPIb binding domain of vWF
Enhanced ristocetin indudced aggregation
decreased HMW multimers
Which type of von willebrand disease is due to loss of function mutations in GPIb binding domain?
type IIM
Prevents binding of vWF to GPIb
Multimer analysis normal
Which type of von willebrand disease is due to missense mutatino in vWF exon 28?
type IIa
Factor 8 and vWF are normal and vWF activity is markedly decreased
Which type of von willebrand disease results from a mutation in domain that binds factor 8?
Type II N
Mimics hemophila A
Which type of von willebrand disease has virtually no vWF?
Type III
frameshift, nonsense or deletion mutation in vWF gene
Low factor 8, vWF antigen and activity
What two groups of patients (besides hemophiliacs) develop antibodies to factor VIII?
elderly
postpartum females
What acquired factor deficiency can you find in patients with amyloidosis?
Factor 10
How does activated protein C inhibit coagulation?
Degrades activated factors 5 and 8
What factors does antithrombin inhibit?
2, 9a, 10a, 11a, 12a
What antibody is present in type 2 HIT?
anti-PF4 antibody
What are two causes of spherocytosis and how do you tell them apart?
- hereditary spherocytosis: ANK1 (ankyrin) mutations
- Autoimmune hemolytic anemia: Positive DAT
Does S/alpha increase or decreased hgbS?
decrease
Does S/beta-thal increase or decrease HbS?
Increase (usually >50% HbS)
HbD is alpha or beta chain defect?
beta
HbG is alpha or beta chain defect?
alpha
Hb Lepore is what sort of hb defect?
fusion between alpha and beta genes
What two CBC parameters are calculated? What is the formula for each?
Hct = MCV x RBC/10
MCHC = Hgb/Hct x 100
Will you have large or small platelets in ITP?
small
What is the half life of factor 13
5-10 days (longest of all coag factors)
