Blood (coagulation) Flashcards
myoglobin vs. hemoglobin
myoglobin: monomer, binds to O2 tightly, for STORAGE
hemoglobin: tetramer, for DELIVERY of O2 to tissues
types of hemoglobin
HbA: normal adult Hb, 2 alpha + 2 beta
HbF: fetal hemoglobin, 2 alpha + 2 gamma
HbA2: 2 alpha + 2 delta
HbM: methemoglobin, cannot bind O2 due to iron oxidized (Fe2+ ==> Fe3+)
HbS: sickle cell anemia, causes intracellular linear polymerization at intravascular areas of low O2 tension
oxygen dissociation curve (ODC) affected by
pH, CO2, temperature, 2,3-DPG
increased [H+], CO2, temp, 2,3-DPG leads to decreased Hb O2 affinity (aka more O2 released to the tissues)
alpha vs. beta thalassemia
alpha thalassemia: decreased alpha chains, leading to free beta/gamma chains (increased levels of HbH, Hb Bart’s)
beta thalassemia: decreased beta chains, leading to increased gamma/delta chains (increased level of HbF, HbA2)
what is a treatment for sickle cell anemia?
hydroxyurea: increases expression of HbF
types of leukocytes
granulocytes:
- neutrophils (phagocytosis)
- eosinophils (parasites)
- basophils (hypersensitivity, rarest WBC)
agranulocytes:
- monocytes (macrophage in tissues, largest WBC)
- lymphocytes (B/T/NK cells)
stages of hemostasis
1. initiation: after endothelial injury, activation and vasoconstriction
2. primary hemostasis: platelet binding, activation, aggregation, granule secretion
3. secondary hemostasis: activation of clotting cascades, polymerization of fibrin
4. resolution: clot resolution, activation of plasmin, thrombolysis
primary hemostasis
vascular hemostasis:
1. vasoconstriction
2. exposure: von Willebrand factor sticks to exposed collagen after injury
platelet plug formation:
1. adhesion: platelet GpIb (glycoprotein Ib) receptors bind to vWF
2. activation: increased GpIIb/IIIa on platelet surface, positive feedback of platelets
3. aggregation: GpIIb/IIIa binds fibrinogen, which corsslinks platelets ==> platelet plug
secondary hemostasis
extrinsic pathway (tissue factor pathway) + intrinsic pathway ==> common pathway ==> fibrin network (thrombus)
phosphatidylserine flip on platelet surface: provides framework for clotting cascades
requires Vitamin K
what are the main steps in:
extrinsic pathway (coagulation)
- activated endothelium expresses tissue factor (TF)
- TF activates VII ==> VIIa
- VIIa activates X ==> Xa
- common pathway
extrinsic pathway defect: prothrombin time (PT) prolonged
what are the main steps in:
intrinsic pathway (coagulation)
in vitro:
1. XII ==> XIIa
2. XIIa activates XI ==> XIa
3. XIa activates IX ==> IXa
4. IXa activates VIII to VIIIa
in vivo:
1. thrombin (IIa) activates VIII ==> VIIIa
then,
VIIIa activates X ==> Xa ==> common pathway
intrinsic pathway defect: activated partial thromboplastin time (APTT) prolonged
common pathway (coagulation)
- Xa cleaves V ==> Va
- Xa/Va activates II ==> IIa (thrombin)
-
IIa cleaves fibrinogen ==> fibrin;
XIIIa crosslinks and stabilizes fibrin network to form thrombus
defect in last step of coagulation cascade: thrombin time (TT) prolonged
thrombosis & embolism
thrombosis: formation of a blood clot in an intact vessel with damaged/activated endothelial cells; always pathogenic
embolism: movement of solid material in blood stream, capable of blocking small vessels
what are the symptoms of
defect in primary hemostasis
- spontaneous bleeding
- skin, mucous membranes affected
- petechiae, ecchymoses (surface-level bruises)
ex: thrombocytopenia, vWB disease, scurvy, platelet defects
what are the symptoms of
defect in secondary hemostasis
- delayed bleeding after trauma
- deep tissue hemorrhage
- hematomas (deep)
- joint, muscle, CNS, retroperitoneal
ex: factor deficiency, drug therapy, chronic liver disease
