RBC II, Putthoff, Hemophilias Flashcards
What is the most common hereditary disease assoc with life threatening bleeding
hemophilia A
what is the mutation in hemophilia A
mutations in facotr VIII
inhertiatnce hemophilia A
X linked recessive
The severity of clinical signs of hemophilia A depends on what
level of facto VIII activity
what percent of VIII activity constitutes moderately severe and mild levels hemophilia A
2-5% is moderately severe
6-50% mild
most mutations with VIII causing hemophilia A are what
inversion involving the X chromosome that abolishes synthesis of factor VIII
If immunoassay levels of VIII are normal is suspected hemophilia A case does this rule it out? why or why not?
no because can have point mutations that impair function
Clinical Sx of hemophilia A
easy bruising and massive hemorrhage after trauma or operative procedures
spontaneous hemorrhages in areas susceptible to trauma, like joints
PT and PTT of hemophilia A
prolonged PTT
normal PT
what does the complex VIIIa/IXa do
activate X
Tx hemophilia A
infusions of recombinant factor VIII
therapeutic challenge in Tx hemophilia A
can develop Ab to the factor VIII since “never seen before”
What is Hemophilia B causedby
factor IX deficiency
clinically indistinguishable from hemophilia A
inheritance hemophlia B
x linked recessibe trait
PT and PTT hemophilia B
PTT prolonged and PT normal
how to Dx hemophilia B
assay of factor levels
Tx hemophilia B
Tx with infusions of recombinant factor IX
What is DIC
acute, subacute or chronic thrombohemorrhagic disorder characterized by the excessive activation of coagulation and the formation of thrombi in the microvasculature of the body
What occurs to blood products in DIC
consumption of platelets, fibrin, coagulation factors
activation of fibrinolysis
Signs and Sx DIC
tissue hypoxia and infarction caused by myriad microthrombi
Is DIC a primary disease
no coagulopathy that occurs in course of variety of clinical conditions
describe clotting in vivo
TF which combines with VII to activate X and IX
X–> thrombin which activates fibrinogen to fibrin which activates IX VIII and V to stimulate crosslinking and activate platelets
what occurs to thrombin at distal sites from acute injury of vessels wall
binds thrombomodulin and becomes an anticoagulant
what does thrombin-thrombomodulin do
activates protein C which inhibits V and VIII
What factor is in blood to decrease blood clots
plasmin
what 2 major mech trigger DIC
release of TF or other procoagulants and widespread injury to endothelial cells
what is a state taht is at high risk DIC
widespread cancer
pregnancy
What is an important mediator of endothelial injury
TNF
DIC is most likely assoc with what
obstetric complications
malignant neoplasms
sepsis
major trauma
how can infections lead to DIC
endotoxins
Ag-Ab complexes that activate C’
what cancers are most freq assoc with DIC
acute promyelocytic leukemia, adenocarcinomas of lung, pancrease, colon and stomach
What are signs DIC
dyspnea, cyanosis, respiratory failure, convulsions, coma, oliguria, acute renal failure
sudden progressive circulatory failure and shock
Dx DIC based on
lab studies
fibrinogen levels
PT and PTT
fibrin split products
what are the consequences of DIC
1) deposition fibrin in microvasculature leading to ischemia and microangiopathic hemolytic anemia from fragmentation RBC
2) consumption of factors leads to hemorrhagic diathesis
What is kasabach-Merritt syndrome
unusual form DIC in assoc with giant hemagiomas
thrombi form in neoplasm because stasis and recurrent trauma to fragile blood vessels
who are more severely affected by hemophilia disorders male or females?
males because only have one X
most common adverse reaction to transufions
febrile nonhemolytic reaction
what are signs febrile nonhemolytic reaction from transfusion
fever chills
mild dyspnea within 6 hrs
what causes febrile nonhemolytic reaction from transufion
inflammatory mediators from donot leukocytes
what is Tx for febrile nonhemolytic reaction
antipyretics
shortlived Sx
When can severe allergic reactions occur after transufion
when blood with Ag is given to previously sensitized patient
most common patients to have severe allergic rxn to transfusion
IgA deficiency
IgG Ab recognize IgA in infused blood
What cause the urticarial allergic reactions after transfusions
donated blood recognized by IgE Ab in recipient
Acute hemolytic reactions to transfusions are caused by what
preformed IgM Ab against donor RBC that fix C’
usually from error in tube labeling (ABO compatability)
IgM Ab in acute hemolytic rxns cause what
C’ mediated lysis, intravascular hemolysis, hemoglobinuria
what are Sx acute hemolytic rxn
fever, shaking chills and flank pain appear rapidly
Dx of acute hemolytic rxn?
direct Coombs test
rapidly progressing acute hemolytic rxn can lead to
DIC shock acute renal failure and death
What are delayted hemolytic reactions to transfusions caused by
Ab that recognize RBC Ag that recipient was previously sensitized to
IgG
Dx delaye hemolytic rxns transfusion
direct coombs
laboratory features of hemolysis: low haptoglobin and elevated LDH
Ab to what Ag can cause severe near fatal reactions from transfusions
Rh Kell and Kidd
activate C’
What is Transfusion related Acute Lung Injury
severe frequently fatal complication from activation of neutrophils in lung microvasculature
What patients are at higher risk for transfusion lung injury
preexisiting lung disease
What is current idea behind trasnfusion lung injury
2 hit hypothesis
1) priming that inc sequestration and sesitization of neutrophils in microvasc of lung
2) neutrophils activated by factor in the trasnfused blood product
What are the most common Ab associated with transfusion acute lung injury
those that bind MHC Ag (MHC I)
usually multiparous women
What types of blood products have higher neutrophil specific Ag
fresh frozen plasma and platelets
what is clnical presentation of transfusion related acute lung injury
dramatic with sudden onset respiratory failure, during or soon after a transfusion
diffuse b/l pulmonary infiltrates that do not respond to diuretics
fever hypotension, hypoxemia
Tx transfusion related lung injury
supportive and outcome is guarded (>50% in severely ill patients)
What type infections are complications in transfusions
infectious-bacterial or viral
significant bacterial infections in transfusions mroe likley in what prepartaion
platelet because stored at room temp
Sx bacterial infection from transfusion
fever chills hypotension
what viruses can be trasnmitted in transfusions
HIV Hep C and B
West nile, trypanosomiasis and babesiosis
