Hemostasis Flashcards
steps in hemostasis
1) blood vessels constrict to slow blood flow
2) platelets aggregate and stick to injured area and to each other
3) coag factors reinforce platelet plug with fibrin clot
4) removal of excess hemostatic material re-establishes integrity
function of vascular system in hemostasis
vasoconstriction, diversion of blood flow, initiate contact with platelets and coag proteins
function of platelets in hemostasis
formation of platelet plug to stop initial bleeding
what stabilizes platelet plug
fibrin formation and thromboplastin
fibrinogen group of coagulation factors
I
V
VIII
XIII
prothrombin group of coagulation factors
II
VII
IX
X
vitamin K dependent coagulation factors
II
VII
IX
X
fibrinogen is factor ___
I
prothrombin is factor ___
II
tissue thromboplastin/tissue factor is factor ___
III
ionic calcium is factor ___
IV
labile factor/proaccelerin is factor ___
V
stable factor (procovertin) is factor ___
VII
antihemophilic factor/von Willebrand factor is factor ___
VIII
Christmas factor/plasma thromboplastin factor ___
IX
Stuart-Prower factor ___
X
plasma thromboplastin antecedent is factor ___
XI
Hageman factor/contact factor ___
XII
fibrin stabilizing factor ___
XIII
product recommended for increased LY30
antifibrinolytic (TXA)
product recommended for decreased MA
platelet
product recommended for decreased angle and increased K
cryo
product recommended for increased R
FFP
symptoms of vitamin K deficiency
easy bruising oozing from nose or gums excessive bleeding heavy periods bleeding from GI tract blood in urine/stool
coag test that measures time it takes for plasma to clot once thromboplastin and calcium are added
prothrombin time
PT measures what pathway?
extrinsic and common
coag test used to monitor warfarin therapy
PT
conditions with prolonged PT
warfarin therapy vitamin K deficiency liver disease acquired or hereditary factor deficiency factor inhibitor drugs or antibodies
coag test that measures times it takes for plasma to clot once activator reagent is added
activated partial thromboplastin time
PTT measures deficiencies in what pathway
intrinsic and common
PT reference range
11-13.5 seconds
PTT reference range
30-40 seconds
coag test used to monitor heparin therapy
PTT
conditions with prolonged PTT
heparin therapy
circulating inhibitors
decreases in circulating levels of II, IX, X in patients on oral anticoagulants
precursor to fibrin which is necessary for clot formation
fibrinogen/factor I
enzyme that converts fibrinogen to fibrin
thrombin
normal fibrinogen level
200-400 mg/dl
how is fibrinogen level measured
excess thrombin added to plasma and clotting time measured
clotting time inversely proportional to fibrinogen concentration
test that measures conversion of fibrinogen to fibrin
thrombin time
normal thrombin time
15-25 seconds
reasons for prolonged thrombin time
low fibrinogen
impaired fibrinogen function
thrombin inhibitors
multiple myeloma
test to aid in determining cause of abnormal/prolonged PT or PTT results in which normal fresh plasma is mixed 1:1 with patient plasma
mixing study
if PT/PTT is corrected in a mixing study, the prolong is due to ___
factor deficiency
is PT/PTT is not corrected in a mixing study the prolong is due to ___
potential factor inhibitor
detects how well platelets stick together
Platelet (Ristocetin) aggregation
abnormal ristocetin aggregation due to:
meds that affect platelet function von Willebrand disease liver disease acute leukemia food consumption (caffeine, garlic, ginger)
test to aid in determining cause of abnormal PT/PTT where patient’s plasma is tested with specific factor deficient substrate plasma
factor assay
factors tested using PT methodology when doing factor assays
II
V
X
factors tested using PTT methodology when doing factor assays
VIII
IX
XI
XII
test that screens for factor XIII deficiency
5M urea lysis (urea solubility)
physiology of 5M urea test
factor XIII crosslinks fibrin to stabilize clot weak clot (fibrin not crosslinked) = clot dissolves normal clots = do not dissolve
steps in fibrinolysis
plasminogen –> plasmin –> breaks down either fibrin or fibrinogen –> fibrin degradation products
function of antithrombin III
blocks abnormal clot formation
fibrin degradation product that allows differentiation between normal fibrinolysis and abnormal clot formation
D-Dimer
normal D-dimer
<0.5 mg/ml
elevated D-dimer indicates excessive ____
clot formation
classic reason for elevated D-dimer
DIC
continual activation of clotting and fibrinolytic cascades
disseminated intravascular coagulation
Lab values in DIC
Prolonged PT and PTT Decreased fibrinogen Increased D-dimer Increased thrombin time Low platelet count
Hemophilia A is deficiency of?
Factor VIII:C
Which hemophilia is “classic” hemophilia?
Hemophilia A
Inheritance pattern of hemophilia A
Sex-linked recessive (X chromosome)
Severe classification of hemophilia A
Less than 1% factor VIII activity
Severe bleeding
Crippling
Needs treatment
Moderate classification of hemophilia A
1-5% factor VIII activity
Occasional hemarthrosis
Treatment needed post-trauma
Mild classification of hemophilia A
6-40% factor VIII activity
Rare hemarthrosis
Fairly normal life
Severe bleeding after dental extraction or other minor surgery
Hemophilia A lab results
Prolonged PTT FVIII decreased PT normal Platelet count normal Ristocetin aggregation normal
Treatment for hemophilia A
Recombinant FVIII
Human plasma derived FVIII
DDAVP for mild cases
Use of Cryo for factor VIII deficiency
No longer used due to excessive donor exposure
Deficiency in von Willebrand disease
VIII:vWF
Difference in deficiency in hemophilia A and von Willebrand disease
Abnormality of FVIII complex different
Most common factor deficiency
Von Willebrand
Von Willebrand bleeding risk when factor activity level is < ___
40%
Blood type correlation with von Willebrand deficiency
Levels vary with blood type
AB > B > A > O
Von Willebrand factor is carrier molecule for what factor
VIII
Symptoms of von Willebrand disease
Mucosal and cutaneous bleeds
Easy bruising
GI bleeding
Menorrhagia
Why is von Willebrand factor essential for platelet function?
Interaction with endothelium
Lab results in von Willebrand disease
PTT prolonged FVIII decreased PT normal Ristocetin aggregation decreased platelet count normal
Treatment of von Willebrand disease
DDAVP
Cryo
Human plasma derived VIII (must contain both FVIII and vWF)
Why is recombinant/monoclonal FVIII not used for von Willebrand disease
Does not contain vWF
Christmas disease is which hemophilia?
B
Factor deficiency in hemophilia B
IX
Inheritance pattern for hemophilia B
sex-linked recessive
Which hemophilia is more common
A
Hemophilia B lab results
PTT prolonged
FIX decreased
PT normal
Platelet count normal
Treatment for hemophilia B
Plasma derived factor IX
Recombinant factor IX
Factors contained in plasma derived prothrombin complex FIX
II
VII
IX
X
Factor I half life
72-120 hours
Factor V half life
12-36 hours
Factor VII half life
5-8 hours
Factor VIII half life
8-12 hours
Von Willebrand half life
22-40 hours
Factor IX half life
48-72 hours
Factor X half life
48-60 hours
Factor XIII half life
72-120 hours
How is factor dosage calculated?
1 unit of factor per kg body weight should raise plasma factor level by ~2%
Half life application if half life is 8-12 hours
~8 hours after infusion the plasma level will drop by 50%
If starting level is 150%, in 8 hours level will be 75%
In 16 hours level will be 37.5%
In 24 hours level will be 18.75%
Causes of fibrinogen deficiency
Liver disease Multiple myeloma Malignancy Inhibitors DIC Surgery OB cases Drugs
Lab results of fibrinogen deficiency
Prolonged PT
Prolonged PTT
Decreased fibrinogen
Treatment of fibrinogen deficiency
Treat underlying cause
Cryo supportive therapy
Prothrombin deficiency causes
Vitamin K deficiency Liver disease DIC GI disease Obstructive jaundice Coumarin drug intoxication
Prothrombin deficiency lab results
Prolonged PT
Prolonged PTT
Decreased FII assay
Treatment for prothrombin deficiency
Vitamin K
Treat underlying cause
FFP supportive therapy
Factor V deficiency causes
Inherited Owren’s disease Parahemophilia Inhibitors DIC Autoimmune disease
Factor V deficiency lab results
Prolonged PT
Prolonged PTT
Decreased FV assay
Treatment for factor V deficiency
Treat underlying cause
FFP supportive therapy
Factor VII deficiency causes
Inhibitors
Liver disease
Coumarin drug therapy
Vitamin K deficiency
Factor VII deficiency lab results
Prolonged PT
Prolonged PTT
Decreased FVII assay
Treatment for factor VII deficiency
Commercial FVII concentrate
FFP supportive therapy
Vitamin K (unless hereditary VII deficiency)
Factor X deficiency causes
Stuart or Stuart-Prower disease
Factor X deficiency lab results
Prolonged PT
Prolonged PTT
Decreased FX assay
Treatment of factor X deficiency
FFP supportive therapy
Vitamin K unless hereditary deficiency
Factor XI deficiency causes
Autosomal recessive disorder, more common in Jewish families
Factor XI deficiency lab results
Normal PT
Prolonged PTT
Decreased FXI assay
Treatment for factor XI deficiency
Usually not necessary
May give FFP if bleeding in surgical situations
Factor XII deficiency causes
Rare autosomal recessive disorder
May exhibit thrombotic episodes later in life
Factor XII deficiency lab results
Normal PT
Prolonged PTT
FXII activated by glass in vivo
Treatment of factor XII deficiency
Not necessary even in surgical bleeding
Factor XIII deficiency causes
Umbilical cord bleeding Poor wound healing Spontaneous abortions Abnormal scar formation Intracranial hemorrhage Oozing from wounds after 36 hours
Factor XIII deficiency lab results
Normal PT
Normal PTT
Normal platelet count
Soluble in 5M urea
Treatment for factor XIII deficiency
Cryo supportive therapy
