RBC and Bleeding Disorders VII Flashcards
inherited disorders of platelet function
defects of adhesion
defects of aggregation
disorders of platelet secretion
bernard soulier
defect in Ib-IX
-vWF receptor
severe bleeding tendency
defectiv in platelet adhesion
glanzmann thrombasthenia
auto recessive
defective IIb-IIIa
no bridging of platelet
defect in aggregation
severe bleeding tendency
disorders of platelet secretion
defective release of thromboxane and ADP
acquired defect in platelet function
aspirin and NSAIDs
cox inhibitors
uremia
acquired defect in platelet function
adhesion granule secretion and aggregation
arachidonic acid metabolism
localized endothelial metabolic sequence associated with tendency to limit bleeding/vasodilation
intrinsic pathway
starts with factor XII
extrinsic pathway
starts with tissue factor to factor VII
prothrombin to thrombin
Xa
thrombin activity
cleaves fibrinogen to fibrin
clotting in vivo
initiated mainly by tissue factor
Hem A
factor VIII
Hem B
factor IX
large posttraumatic ecchymoses or hematomas, prolonged bleeding after surgery/laceration
coag factor deficiency
GI bleeds, GU bleeds, hemarthrosis
coag factor deficiency
patient oozes blood days after tooth extraction
coag factor deficiency
most common deficiency in coag factors
Hem A, Hem B, vWD
vit K deficiency
impaired synthesis of 2, 7, 9, 10 and protein C
DIC
consumption of multiple coag factors
two most common inherited bleeding disorders
Hem A and vWD
synthesis of factor VIII
sinusoidal endo cells and kupffer cells in liver
factor VIII in circulation
binds vWF
stabilizes and extends half life from 2 hours to 12 hours
ristocentin agglutination test
measure of vWF function
causes clumping
inital binding of vWE to endothelial
GpIb
bridging of fibrinogen in platelet aggregation
GpIIb/IIIa
most common inherited bleeding disorder of humans
vWD
mild bleeding tendency - surgery or dental procedure
spontaneuous epistaxis
auto domimant
three categories of vWD
type 1 and 3 - quantitative
type 2 - qualitative
type I vWD
auto dominant
-quantitative defect
70% of cases
mild disease
point substitutions
-rapid clearance from plasma
type III vWD
auto recessive
-quantitative defect
severe clinically - very low vWF
effects factor VIII stability
deletions or frameshift mutations of both alleles
type II vWD
qualitative defect
-2A - most common form
auto dominant
missense mutations - defective multimer assembly
25% of cases
mild to moderate bleeding
vWD clinical
prolonged PTT - due to lack of factor VIII stability
reduced vWF - measured by ristocetin
desmopressin
tx of vWD patient undergoing surgery or dental work
causes vWF release
most common hereditary disease associated with life-threatening bleeding
Hemophilia A
mutation in factor VIII
X-linked recessive
affects mainly males
hem A
mutation in factor VIII
X-linked recessive
affects mainly males
rarely in females - inactivation- unfavorable lyonization
<1% Factor VIII
severe Hem A
2-5% factor VIII
moderately severe Hem A
> 6% factor VIII
mild disease Hem A
most severe deficiency of factor VIII
involve inversion involving X-chromosome that completely abolishes the synthesis of factor VIII
easy bruising, massive hemorrhage after trauma, hemarthroses, NO petechiae
hem A
prolonged PTT and normal PT
hem A
defect in intrinsic pathway
diagnosis of Hem A
factor VIII specific assays
Tx Hem A
infusion of recombinant factor VIII
15% patients with severe disease- develop Abs that bind factor VIII
also risk of HIV transfusion has been almost eliminated
christmas disease
Hem B
factor IX deficiency
clinically indistinguishable from Hem A
X-linked recessive
PTT prolonged and PT normal
diagnosis of christmas disease
only possibly by assay of factor levels
tx of Christmas disease
infusion of recombinant factor IX
hypoxia and infarction as well as hemorrhage
DIC
deposition of microthrombi as well as depletion of heme factors
DIC
not primary disease
coagulopathy occuring in course of variety of clinical condition
activation of factor X
generation of thrombin
thrombin converts fibrinogen to fibrin
thrombomodulin
binds and inactivates thrombin
this complex binds and activates protein C
-inhibitor of factors V and VIII
mechanisms triggering DIC
widespread injury to endo cells
release of tissue factor
mucus from adenocarcinomas
procoagulant - can initiate DIC
TNF
induces endo cells to express tissue factor - can lead to sepsis
causes of CID
most likely obstetric complications
malignant neoplasms
sepsis
major trauma
bacterial infection
endotoxins inhibit expression of thrombomondulin
-to DIC
massive trauma
release of tissue factor
-to DIC
consequences of DIC
deposition of fibrin within microcirculation
-can lead to ischemia and microangiopathic hemolytic anemia
consumption of platelets and clotting factors - hemorrhagic diathesis
plasmin
cleaves fibrin and digests factor V and VIII
bilateral renal cortical necrosis
imcroinfarcts from DIC
waterhouse friedrishsen syndrome
massive adrenal hemorrhage
-with DIC from meningococcemia infection
kasabasch merritt syndrome
form of DIC with giant hemangiomas
thrombin form with neoplasm
DIC clinical
acute - endotoxic shock or amniotic fluid embolism
chronic - carcinomatosis or retention of dead fetus
50% are obstetric patient with pregnancy complications
disorder reversible with delivery of fetus
33% carcinomatosis
microangiopathic hemolytic anemia, dyspnea, cyanosis, resp failure, convulsions coma, oliguria, acute renal failure, circ failure and shock
DIC
acute DIC
bleeding
chronic DIC
thrombotic complications
dx of DIC
fibrinogen, PT, PTT, platelets, fibrin split products
preformed IgM Abs against donor red cells
acute hemolytic rxn
mislabeled blood transfusion
direct coombs test positive
fever, shaking chills, flank pain with positive direct coombs
acute hemolytic anemia
delayed hemolytic reactions
Abs that recognize RBC antigens that recipient was sensitized to previously
-ex prior blood transfusion
typically IgG bs
positive direct coombs
low haptoglobin
elevated LDH
low haptoglobin
hemolysis
TRALI
transfusion related acute lung injury
factors in transfused blood product trigger activation of neutros in lung microvasculature
rare
more frequent preexisting lung conditions
TRALI two hit hypothesis
first - increased sequestration and sensitization of neutros in lungs
second hit - primed neutros are activated by something in transfused blood
-Abs in transfused blood that recognizes Ags on neutros
MHC class I Ags - in multiparous women
sudden onset of respiratory failure soon after transfusion
TRALI
diffuse bilateral infiltrates DO NOT respond to diuretics
also fever, hypotension, hypoxemia
67% mortality in severe cases
bacterial transfusion infections
skin flora
-staph and strep
platelet preparations
stored at room temp
-more likely to grow bacteria
viral transfusion infections
rare - but if virus not detectable with nucleic acid testing
HIV, Hep B, Hep A
most common - is Hep B
low risk of exotic infections - west nile, trypsanosomiasis and babesiosis
