Hemorrhagic Disorders and Laboratory Asssessment Flashcards
Bleeding from a single location
localized bleeding or localized hemorrhage
Bleeding from multiple sites, spontaneous and recurring bleeds, or a hemorrhage that requires physical intervention
generalized bleeding
skin may appear as petechiae, red pinpoint spots (Figure 38.1A); purpura, purple skin lesions greater than 3 mm diameter (Figure 38.1B); or ecchymoses (bruises) greater than 1 cm, typically seen after trauma
mucocutaneous bleeding
Anemia associated with chronic bleeding or a hemolytic anemia; bone marrow response
Hemoglobin, hematocrit; reticulocyte count
assess Thrombocytopenia
platelet count
assess Clotting time prolonged in deficiencies of factors II (prothrombin), V, VII, or X
PROTHROMBIN TIME
Clotting time prolonged in deficiencies of all factors except VII and XIII
Partial thromboplastin time (PTT)
Prolonged by unfractionated heparin therapy, dysfibrinogenemia, hypofibrinogenemia, and afibrinogenemia; qualitative
Thrombin time (TT)
Reduced in dysfibrinogenemia, hypofibrinogenemia, and afibrinogenemia; quantitative result
Fibrinogen assay (FG)
If a patient’s bleeding episodes begin after childhood, are associated with some disease or physical trauma, and are not duplicated in relatives
ACQUIRED
uncommon, occur- ring in fewer than 1 per 100 people, and are usually diagnosed in infancy or during the first years of life.
Congenital hemorrhagic disorders
Defined as any single or multiple coagulation factor or platelet deficiency, and TIC is triggered by the combination of injury-related acute inflammation, hypo- thermia, acidosis, and hypoperfusion (poor distribution of blood to tissues associated with low blood pressure), all of which are elements of systemic shock
Coagulopathy
ADAMTS13
a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13;
15 to 20 mL cryoprecipitate unit provide
150-250 mg of fibrinogen
A target fibrinogen level of should be maintained,
100 mg/dL
Enlarged and collat- eral esophageal vessels called
esophageal varices
unaffected by standard unfractionated heparin therapy and can be used to assess fibrinogen function even when there is heparin in the specimen.
reptilase time test
Acquired autoantibodies that specifically inhibit factors
II (pro- thrombin), V, VIII, IX, and XIII and VWF
confirm the presence of the inhibitor.
Clot-based mixing studies
early rapid loss of factor VIII activity, residual activity remains, which indicates that the reaction has reached equilibrium.
type II kinetics
Quantitation of autoanti-VIII inhibitor is accomplished us- ing the
Nijmegen-Bethesda assay
Autoanti-factor XIII has been documented in patients receiving isoniazid treatment
tuberculosis
most prevalent inherited mucocutaneous bleed- ing disorder
VWD
Domain A supports a receptor site for collagen and a binding site (ligand) for platelet receptor
Glycoprotein (GP) Ib/IX/V and heparin
Domain C provides a site that binds platelet receptor
GPIIb/IIIa
domain D provides the carrier site for
factor VIII
D’D3
FVIII
A1
GP1B
A2
ADAMTS13
A3
COLLAGEN
C1-C6
GPIIB/IIIA
Customary designation for the combination of factor VIII and VWF.
FVIII/VWF
Procoagulant factor VIII, transported on VWF. Factor VIII binds activated factor IX to form the complex of VIIIa-IXa, which digests and activates factor X. Factor VIII deficiency is called
HEMOPHILIA A
Epitope that is the antigenic target for the VWF immunoassay.
VWF:Ag
Factor VIII coagulant activity as measured in a clot- based factor assay.
FVIII:C
Quantitative ristocetin cofactor activity, also called
VWF activity
quantitative VWF deficiency caused by one of several autosomal domi- nant frameshifts, nonsense mutations, or deletions that may occur anywhere in the VWF gene.
type 1
qualitative VWF abnormalities. VWF levels may be normal or moderately decreased, but VWF function is consistently reduced.
type 2
which arises from well-characterized autosomal dominant point mutations in the A2 and D1 structural domains of the VWF molecule.
subtype 2a
mutations render VWF susceptible to increased proteoly- sis by ADAMTS13, which leads to a predominance of small- molecular-weight plasma multimers
subtype 2a
mutations within the A1 domain raise the affinity of VWF for platelet GPIb/IX/V, its customary binding site; these are hence “gain-of-function” muta- tions.
subtype 2b
A platelet mutation that raises GPIb affinity for normal HMW-VWF multimers creates a clinically similar disorder called
platelet-type VWD (PT-VWD) or pseudo-VWD.
qualitative VWF variant that possesses poor platelet receptor binding despite generating a normal multimeric distri- bution pattern in electrophoresis
subtype 2m
autosomal VWF gene missense mutation in the D9 domain impairs the protein’s factor VIII binding site function.
subtype 2N
“Nullallele”VWFgenetrans- lation or deletion mutations that may occur anywhere on the gene produce severe mucocutaneous and anatomic hemorrhage in compound heterozygotes or, in consanguinity, homozygotes.
type 3
most prominent mem- ber of the primary VWD laboratory profile
quantitative VWF:Ag assay
The traditional VWF:RCo assay employs
ristocetin
added to in vitro patient plasma where it unfolds the VWF molecule and reduces repelling negative charges, enabling HMW-VWF multimers to bind reagent platelet membrane GPIb/IX/V re- ceptors.
ristocetin
The VWF:RCo assay, typically performed using a
platelet aggregometer,
PRICE
protection, rest, ice, com- pression, and elevation
When the coagulation cascade is activated, thrombin cleaves plasma FVIII and releases a large polypeptide called the
B domain
