DISORDERS OF SECONDARY HEMOSTAS Flashcards
is a severe form of bleeding that requires immediate intervention and transfusion
hemorrhage
what are the inherited disorders of coagulation: intrinsic pathway disorders
prekallikrein (fletcher factor deficiency)
high molecular weight kininogen (fitzgerald factor) deficiency
factor XI deficiency (hemophilia C; rosenthal syndrome)
Factor VIII;C deficiency (hemophilia A; classic hemophilia)
Factor IX deficiency (hemophilia B; christmas disease)
von willebrand’s disease
what are the inherited disorders of coagulation: extrinsic and common pathway disorders
factor VII (proconvertin; stable factor) deficiency
factor X (stuart-power factor) deficiency
Factor V deficiency (owren’s disease; labile factor deficiency
Factor II (Prothrombin) Deficiency
Fibrinogen (factor I) deficiency
Factor XIII (fibrin stabilizing factor) deficiency
acquired disorders of coagulation
hepatic disease
vitamin K deficiency
therapeutic anticoagulation
circulating anticoagulant (inhibitory) substance
massive transfusion effects
disseminated intravascular coagulation
pre-kallikrein (fletcher factor) deficiency is believed to be transmitted as _____ trait
autosomal recessive trait
laboratory findings of prekallikrein (fletcher factor) deficiency is similar to what factor deficiency
factor XII deficiency
laboratory findings of prekallikrein is similar to factor XII deficiency except for
APTT result as it is shortened if the plasma is incubated with a surface activating substance
what is the surface activating substance being talk about in shortened APTT result of incubated plasma
kaolin
refers to the absence of HMWK in poor contact-phase reactions, a deficiency of kinin formation (active forms derived from kininogen), and defective fibrinolysis reaction
High Molecular Weight Kininogen (Fitzgerald
Factor) Deficiency
active form derived from kininogen
kinin
lab findings in High Molecular Weight Kininogen (Fitzgerald
Factor) Deficiency
APTT results typically are prolonged
other tests are within normal limits
factor XI deficiency is what type of hemophilia
hemophilia C
hemophilia C, what is the general name
rosenthal syndrome
factor XI deficiency is originally describe on what year
1953
factor XI deficiency
what is the mode of inheritance
autosomal dominant
describe the bleeding of factor XI deficiency
mild to moderate bleeding
TX of factor XI deficiency( Hemophilia C; Rosenthal Syndrome
fresh plasma infusions
this deficiency represents the first inherited disorder of the intrinsic cascade to which a clinical bleeding syndrome is attributed
factor XI deficiency (Rosenthal syndrome; hemophilia C)
this deficiency is very prevalent in jewish population
Factor XI Deficiency (Hemophilia C; Rosenthal Syndrome)
clinical findings of patients with factor XI Deficiency (Hemophilia C; Rosenthal Syndrome))
- patients present mild bleeding tendencies which usually respond to therapy
- most patients are symptomatically “silent” until stressed by trauma or surgery
- clinical syndromes may include episodes of epistaxis, hematuria, and menorrhagia
laboratory findings of Factor XI Deficiency (Hemophilia C; Rosenthal Syndrome)
prolonged APTT which is corrected by aged serum
one stage PT and bleeding time are not affected
prolonged aptt in factor XI deficiency is corrected using
aged serum
therapy for Factor XI Deficiency (Hemophilia C;
Rosenthal Syndrome)
no specific blood component exist to treat factor XI deficiency
factor VIII:C deficiency (hemophilia A; classic hemophilia )
is first scientifically described on what year
1803
factor VIII:C deficiency ; hemophilia A; classic hemophilia
what is the disease called
royal disease
mode of inheritance of factor VIII:C deficiency hemophilia A; classic hemophilia
sex-linked (X chromosome)
mother to son
the entire molecule as it circulates in the plasma. Composed of VIII:C and VIII:vWF portions noncovalently bound
VIII/vWF
portion of molecule responsible for binding to endothelium and supporting normal platelet adhesion and function. Tested by bleeding time
VIII:vWF
portions of molecule acting in intrinsic system as cofactor to factor Ixa (with Ca++) in the conversion of factor X to Xa. Tested by PTT
VIII:C
antigenic property of procoagulant portion as measured by immunologic monoclonal antibody techniques
VIIC:Ag
Factor VIII-related antigen, which is a property of the large vWF portion of
the molecule and measured by immunologic techniques of Laurell rocket or
immunoradiometric assay.
VIIIR:Ag
Ristocetin cofactor activity, which is factor VIII related activity required for
aggregation of human platelets with ristocetin in in vivo aggregation studies
VIIIR:RCo
Bleeding diathesis arises from decreased or defective factor VIII:C.
Hemophilia A
Joints of the knee, elbow, ankle and shoulder are the most vulnerable
parts of the patient
Hemophilia A
Repeated hemarthroses can cripple and deform the patient.
Hemophilia A
✓Tragically, 70% of hemophiliacs treated before 1984 are ___ and
have died from ___
HIV positive and
have died from AIDS
lab findings of hemophilia A
prolonged APTT but corrected by adsorbed plasma but not with aged serum
level so of factor VIII:C differ in the daughters of
carrier females (maternal carrier) and the daughters
of hemophiliacs (paternal carriers).
__ product infusion to replace factor VIII:C
Cryoprecipitate
hemophilia A
For milder cases, administration of pharmacologic agent such
as __ may be
substituted for donor component.
1-desamino-8-D-arginine-vasopressin (DDAVP)
hemophilia A
Intravenous administration of DDAVP rise plasma levels of
plasma factor VIII:C how manytimes
threefolds to sixfolds
used to monitor therapeutic progress of
patients with hemophilia A
factor assays
Patients who have developed antibodies against factor VIII:C
may be given with ____ component to purge the antibody from plasma. But this was believed to be ineffective
plasma pheresed
__ components are
used or reserved especially for life threatening situations.
Porcine factor VIII:C and prothrombin factor
Factor IX Deficiency is also called as
hemophilia B; Christmas disease
Factor IX Deficiency represents approx ____ of hemophilia cases in the US
14%
Milder form of hemophilia than factor VIII:C deficiency
Factor IX Deficiency (Hemophilia B; Christmas Disease
- Deficiency reduces thrombin production and may lead to soft tissue bleeding that is indistinguishable from
hemophilia A.
Factor IX Deficiency (Hemophilia B; Christmas Disease)
Three variants of the factor IX deficiency based on antigenic reactivity
of it:
cross reactive material positive (CRM+)
cross reactive material negative (CRM-)
cross reactive material reduced (CRMr)
lab findings of hemophilia B
prolonged aptt which is corrected with aged serum but with not adsorbed plasma
specific factor IX assay - used for diagnosis and to assess actvity levels during therapy
therapy for hemophilia B
administration of commercial concentrate products
plasma exchange with normal donor plasma have been performed to achieved 50% to 100% activity levels and to prevent cardiac overload
Factor XI Deficiency (Hemophilia C; Rosenthal
Syndrome)
mode of inheritance
autosomal dominant hemophilia
year 1926, ____ described this disorder at autosomal dominant disorder that produces a prolonged bleeding time and evidence of vascular fragility
eric von willebrand
Caused by defects in both in factor VIII:C and VIIIR:Ag of factor VIII complex.
von willebrand disease
In 1971, __ demonstrated that the vWF portion
of the VIII complex is reduced or absent in von willebrand disease
Zimmerman
Platelets in von Willebrand’s plasma, in contrast to platelets in normal plasma, do not aggregate in the presence of __.
ristocetin
Patients demonstrate easy bruisability, epistaxis, menorrhagia and hemorrhage from tooth extraction
von Willebrand’s Disease
It is the most frequently inherited disorder.
von Willebrand’s Disease
type of von willebrand disease
homozygous “double heterozygous”
heterozygous I
heterozygous II (subtype IIa IIb)
from the type of von willebrand disease, which one is the autosomal recessive
homozygous
from the type of von willebrand disease, which one has the a severe effect
homozygous
effect of heterozygous von willebrand disease
variably; mild to moderate
effect of heterozygous II
variable
a predominant plasma protein of the extrinsic coagulation pathway
factor VII (proconvertin; stable factor) deficiency
mode of inheritance of factor VII (Proconvertin; Stable Factor) deficiency
autosomal recessive genetic abnormality with intermediate expression
a very rare disorder that occurs in 1 every 500,000 individuals
Factor VII (Proconvertin; Stable Factor) Deficiency
what are the variants of Factor VII (Proconvertin; Stable Factor) Deficiency
CRM+ AND CRIM R
no negative in factor VII deficiency
In factor VII deficiency, the Correlation between ___ and ___ are poor.
clinical tendency and activity
levels
patients are vulnerable to thrombotic events
Factor VII (Proconvertin; Stable Factor) Deficiency
lab findings of factor VII deficiency
diagnosis is based on family history
prolonged PT
normal thrombin clotting time and APTT
chromogenic substrate procedures measure the ability of factor VII to cleave factor X
increased levels of factor X in pregnant women
therapy for factor VII deficiency
Infusion of donor plasma, serum components or commercial concentrates containing prothrombin complex (Autoplex T preparations).
it is inherited as autosomal trait that is incomplete recessive but shows high penetrance
factor X (stuart-prower factor) deficiency
factor X (stuart-prower factor) deficiency
does it have immune variants?
yes
the disorder is uncommon in the general population
factor X - stuart prower deficiency
in Factor X (Stuart- Prower Factor) Deficiency,
the symptoms of patients having the disorder are variable
true or false
true
lab findings of Factor X (Stuart- Prower Factor) Deficiency
prolonged APTT, PT, and stypven time
prothrombin utilization is abnormal
PT is corrected by aged serum but not with adsorbed plasma
Therapy for factor X deficiency
✓FFP or Prothrombin complex concentrates are used for therapy
Factor V Deficiency, what’s the disease called?
owren’s disease; labile factor deficiency
Factor V Deficiency (Owren’s Disease; Labile Factor Deficiency)
discovered in 1944 by
Professor Owen
mode of inheritance of factor V deficiency
autosomal recessive
also described as deficient in conjunction with factor VIII deficiency due to genetic defect traced to chromosome 18
Factor V Deficiency (Owren’s Disease; Labile Factor Deficiency)
FACTOR V LAIDEN MUTATION (_______)
it’s like some sort of code
R506Q
In 1993, a new and very common inherited
thrombophilic syndrome was described:
activated protein C resistance (APCR)
FACTOR V LAIDEN MUTATION (R506Q)
Molecular defect (single point mutation) was identified involving the transition of a guanine (G) to adenine (A) at nucleotide __
1691 of factor V gene.
FACTOR V LAIDEN MUTATION (R506Q)
Mutation results in the substitution of __at number 506
arginine (R) with glutamine (Glu)
factor V laiden mutation
Screening for the presence of APCR is easily performed
by clottable assays utilizing __
modified APTT & Russell’s
viper venom time methods.
- May be inherited as a deficiency or a
dysfunction.
Factor II (Prothrombin) Deficiency
Hemarthroses in patients are rare
Factor II (Prothrombin) Deficiency
Factor II (Prothrombin) Deficiency
can aspirin be administered
nope, can cause serious bleeding
lab findings for Factor II (Prothrombin) Deficiency
▪ APTT & one-stage PT will be prolonged.
▪ TCT (Thrombin clotting time) is normal.
▪ Two-stage prothrombin method and immune based factor assay using antiprothrombin antisera are the
diagnostic test procedures.
therapy for Factor II deficiency
➢Infusion of FFP is the usual choice of treatment.
➢Vitamin K concentrates may also be given to patients but there is a risk of thrombosis after administration
FibrInogen (Factor I) Deficiency
defect may result to the following conditions
afibrinogenemia
hypofibrinogenemia
dysfibrinogenemia
–inherited lack of fibrinogen.
Afibrinogenemia
inherited deficiency of fibrinogen.
Hypofibrinogenemia
–inherited production of dysfunctional
fibrinogen molecule.
Dysfibrinogenemia
____ __ aid in the differentiation
between inherited and acquired forms of fibrinogen deficiency
History and clinical features
AFIBRINOGENEMIA
mode of inheritance
recessive and severe condition
Patients having this condition have nearly undetectable
amounts of fibrinogen
AFIBRINOGENEMIA
- Patients’ platelets appear affected in that prolonged bleeding time may be measured. (Platelets have a
surface receptor for fibrInogen, and fibrinogen
apparently is necessary for platelets to function in vivo)
AFIBRINOGENEMIA
LABORATORY FINDINGS of afibrinogenemia
▪ Prolonged bleeding time, PT, APTT & TT
▪ Abnormal platelet adhesion and aggregation
therapy for afibrinogenemia
➢Treatment requires administration of
cryoprecipitate
➢FFP may be used; however, volume overload is a
major concern.
➢Whole blood transfusions may be required if
significant bleeding has occurred.
Patients possess 20-100 mg/dL level of fibrinogen
(normal range: 200-400 mg/dL).
HYPOFIBRINOGENEMIA
mode of inheritance of hypofibrinogenemia
Inherited as heterozygous, autosomal recessive
disorder.
TX FOR hypofibrinogenemia
Cryoprecipitate & FFP are the treatment of choice for
this condition
Molecular structure of fibrinogen is said to be normal for what type of fibrinogen deficiency
hypo and afib
mode of inheritance of dysfibrinogenemia
Inherited as an autosomal dominant trait
Patients demonstrate abnormal fibrinogen function but usually
have normal levels in antigenic assay.
DYSFIBRINOGENEMIA
- Substitution of amino acids in fibrinogen’s polypeptide chains is the striking feature of dysfibrinogenemia, which may result in:
- Inability to submit proteolysis by thrombin, because the cleavage sites are inappropriate.
- Peculiar behaviour during polymerization stages secondary to aberrant charge distribution across the molecule.
- Addition of inappropriate side groups that affect reactivity.
- Persistence of fetal fibrinogen into adulthood
lab findings for dysfibrinogenemia
▪ Normal PT, APTT
▪ Normal bleeding time and platelet function tests
▪ Normal quantitative level of fibrinogen
▪ Mild to markedly prolonged thrombin time
▪ Prolonged ReptilaseR
(venom) clotting time.
Factor XIII (Fibrin-Stabilizing Factor) Deficiency
mode of inheritance
autosomal recessive trait in which only homozygotes express the syndrome
- Patients exhibit spontaneous bleeding and poor wound
healing processes with unusual scar formation
Factor XIII (Fibrin-Stabilizing Factor) Deficiency
Factor XIII (Fibrin-Stabilizing Factor) Deficiency
all patients should avoid what medication
aspirin
lab findings for factor XIII deficiency
▪ Patients have inadequate cross-linking of fibrin which
results in an unstable and friable clot with excessive
red cell “fall out”.
▪ Condition cannot be evaluated in the presence of
heparin
▪ Specific Factor XIII assays are available but are not
suitable for routine clinical use.
▪ Immunologic Factor XIII procedures are available to
measure quantities of the said factor
therapy for factor XIII deficiency
➢Infusion of donor plasma or commercial purified, lyophilized placental factor XIII.
Liver disorders present two challenges
decreased synthesis of coagulation, lyses, and inhibitory proteins
impaired clearance of activated hemostatic component
there is a decreased level of
plasma contact factors secondary to hepatic immaturity
Neonatal hepatic disease
Neonatal hepatic disease resultsto
there is a decreased level of
plasma contact factors secondary to hepatic immaturity
insufficient levels of antithrombiin III and plasminogen
expression of a unique fetal fibrinogen which behaves differently as to matured ones
is produce by normal flora of the GIT and
absorbed.
vitamin K
vitamin K deficiency is due to
absence of normal flora in GIT due to intake of broad spectrum antibiotics
absorption is decreased as seen in obstructive jaundice
if antagonistic drug like coumarin us taken by the patient
is used to asses levels of vitamin K dependent factors in the new born
one stage PT
Intravenous anticoagulant most commonly used in clinical medicine
heparin
- It is used extensively in preventing fibrin deposition
on intravenous tubing devices residing in vessels.
heparin
It is a mucopolysaccharide that acts in conjunction
with antithrombin III to inhibit most of serine
proteases in the coagulation pathways.
heparin
heparin
- It is metabolized by the liver and has a half-life of approximately ____ hours
3 hrs
Coumarin Drugs (Oral anticoagulants)
* Discovered in __
Wisconsin
is most frequently used coumarin which is
water soluble and administered orally
warfarin
It interferes with the carboxylation of vitamin K dependent
procoagulants in the liver by interrupting the
enzymatic phase of this reaction.
coumarin drugs
Nonfunctional proteins that circulates in the plasma as a result of warfarin activity is referred to as
proteins induced by vitamin K antagonist (PIVKA)
substance produced by the
body that inhibit coagulation
Circulating anticoagulant
circulating anticoagulant’s Stimuli include
infusion of blood or blood products,
release of tumor substances into the circulation and
autoimmune disorders
Patients having this kind of circulating anticoagulant have increased levels of fibrinogen (as seen in ___)
DIC, coagulation and lytic disorders
laboratory testing for circulating anticoagulant (inhibitory) substance includes
FSP agglutination test,
measurement of fibrin monomers,
platelet counts,
fibrnogen levels, APTT & PT.
Massive transfusion can jeopardize hemostatic competency because:
excessive quantities of infused citrates
donor product is incompatible to recipient’s system
deficient labile clotting factors or platelets in stored blood
is considered as sensitive indicator of
depressed platelet function in extensively transfused
patients
bleeding time
are less sensitive but useful in deciding
whether to supplement therapy with cryoprecipitate
or FFP in masiive transfusion effect
APTT and PT
A complication of other primary disorders.
Disseminated Intravascular Coagulation
- It results in consumption of coagulation proteins and
platelets into thrombi which are deposited locally or
widely in the circulation.
Disseminated Intravascular Coagulation
do Disseminated Intravascular Coagulation has age preference?
no age or gender preference for this disorder
acute Disseminated Intravascular Coagulation has a mortality of
60-80%
progress of DIC may be controlled by
plasmin or thrombin
lab result of Disseminated Intravascular Coagulation reveals
prolonged APTT, TCT, PT
decrease PLT COUNT, FIBRINOGEN LEVEL, ANTITHROMBIN III,
elevated FSP and FIBRIN MONOMERS and POSITIVE D-DIMER
THERAPY for DIC
replacement therapy with blood components are necessary following acute DIC
Infusion of FFP, PC, and CRYOPRECIPITATE may be used
complete profile of coagulation and lysis should be performed at clinically determined intervals to assess this syndrome during management
