hemostasis and thrombosis Flashcards
1
Q
what is hemostasis
A
Ability to maintain blood in a fluid state and prevent loss
2
Q
what are the 3 major components of hemostatic system
A
Vascular wall
Platelets
Coagulation proteins
3
Q
how does vascular injury seal off the damged site to prevent futher blood loss
A
Exposes subendo collagen
- activated platelets
- activates coagulation proteins to create a more stable mesh with platelet plus
4
Q
what is the primary hemostatic plug
A
the intial platelets coming together
5
Q
what are the two aspects of hemostatic balance
A
Procoagulant
Regulatory
6
Q
what is the first part of the platelet response
A
Adhesion of platelets to damaged endothelial site
7
Q
what is needed for adhesion of platelets
A
surface membrane receptor (glycoprotein Ib/IX) adhesive protein (von willbrand factor) appropriate surface (subendo collagen)
8
Q
what is the roll of vWF
A
mediates adherence of platelets to subendo collagen
9
Q
what happens when platelts are bound to vWF
A
become activated release second messenger molecules shape change from discoid to spherical secrete cytoplasmic ADP activate glycoprotein IIb//IIIa recetpor
10
Q
what mediates contraction of the platelet
A
actin fibers
11
Q
what does release of cytoplasmic ADP into the local milieu by activated platelets do
A
activate adjectent platelets
12
Q
what mediates platelet to platelet bind
A
Fibrinogen
gp IIb/IIIa receptor
13
Q
what happens when soluble coagulation proteins within plasma is activated
A
Generate thrombin in an amplification reaction
14
Q
what does thrombin to
A
converts fibrinogen to fibrin
15
Q
what is the roll of fibrin
A
adds stability to the clot after fibrin monomers by covalently crosslinking by factor XIII
16
Q
what is the intrinsic pathway
A
sequence of activation of Factor XII by kalikrein
activation of factor XI by factor XIIa
17
Q
what is the extrinsic pathway
A
sequence of activation of factor VII by tissue factor
18
Q
what is the common pathway
A
activation of X to Xa
conversion of prothrombin (II) to thrombin
conversion of fibrinogen to fibrin
19
Q
how is a fibrin clot formed
A
fibrin monomers generated by thrombin polymerize to form a long strand
20
Q
what makes the fibrin monomers stable
A
covalent crosslinking by factor XIII
21
Q
what does primary hemostasis regulate
A
platelets
22
Q
what does secondary hemostasis regulate
A
coagulation pathways
23
Q
what molecules regulate primary hemostasis
A
NO
Prostacyclin (PGI2)
ADPase
24
Q
what molecules regulate secondary hemostasis
A
Serine protease inhibitors (antithrombin)
protein C pathway (Controls Va and VIIIa)
fibrinolytic system (removes excess clot)
25
how does antithrombin regulate secondary hemostasis
Inhibit activity of thrombin and other serine proteases of the coagulation cascade by forming inactive enzyme-inhibitor complex
26
what is the action of antithrombin III in the presence of heparin
becomes activated so that it can form a complex with thrombin
- desotrys thrombin's ability to participate in generation of fibrin monomers
27
what does Protein C regualte specifically
Factors Va and VIIIa
28
what are the parts of the protein C system( major effecor and coenzyme
Protein C: major effector
| Protein S: major cofactor
29
what do protein C and S deficincies lead to
Hypercoaguable states
30
what does Factor V leiden mutation lead to
Promotes coagulation
31
what does tissue plasminogen activator do in presence of fibrin
Binds to plasminogen and converts it to active enzyme plasmin
32
what does active plasmin do
breaks down previsouly cross linked fibrin into fibrin degradation prodcuts
- breaks down previously formed clot
33
what does uncontrolled activation of plasmin lead to
bleeding complicactions
34
when is a TPA infusion done
recent myocardial infarcts
35
what tests are done for hemostasis
```
Prothrombin time
international normalised ratio
partial thromboplastin time
platelet cound
bleeding time
```
36
what does prothrombin time screen for
Activity of proteins in the extrinsic pathway (factors V, VII, II, X, and fibrinogen)
37
what is done in a prothrombin time test
Phospholipid and tissue factor added to patient's plasma with Ca++
- time noted for a clot(11-13 sec)
38
what does partial thromboplastin time screen for
actiivity in the intrinsic pathway (factors XII, XI, IX, VIII, X, V, II, and fibrinogen
39
what is done in a partial thromboplastin time tests
addition of negatively charged activator of factor XII to patient serum with Ca++
- clot form after 28-35 sec
40
when do we tend to do partial thromboplastin time
monitor patients on heparin
41
what does a problem being corrected in a mixing study show about hemostasis
PAtient deficiency exists
42
what happens if their is no correction of hemostasis in a mixing study
Inhibitor is present( factor specific or lupus anticoagulant type)
43
what is the most important part of defining the cause of a bleeding disorder
Careful clinical history
- bleeding manifestation (evidence and nature of bleeding)
- age of onset of symptoms
- bleeding frequecy
- family history
- med history
- predisposing causes
44
what kind of patient do you use prothrombin time on
patients with oral anticoagulants
45
how is a mixing study done
mix 50:50 with patient plasma and extra plasma
- if a change in the PT and PTT test occurs a deficiency of some factors is present
- if no hange, inhibitor is present, either factor specfic of lupus anticoagulant
46
how are congenital dissorders developed
hereditated and seen at birth
47
when do acquired disorders appear
after birth
48
what causes acquired disorders to come to be
Meds
| pathologic processes
49
how do disorders of primary hemostasis manifest clinically
mucocutaneous bleeding
| bleeding associated with trauma
50
hwo do disorders of primary hemostasis manifest laboratory
prolonged bleedingtime/PFA-100
| thrombocytopenia
51
how do secondary hemostasis disorders manifest clincally
soft tissue bleeding
| bleeding associated with trauma
52
how do secondary hemostasis disorder manifest clinically
include prolonged PT/PTT/thrombin time
53
what are the clinical manifestation of disorders of the regulatory system
Soft tissue bleeding
| Bleeding associated with trauma
54
what are the laboratory manifestations of disorders of the regulatory system
Normal in screening tests
55
how is von willebrand disease transmitted
Autosomal dominant disorder (usually)
56
what does von willebrand disease result for
abnormalities of vW factor (wuantitiative, qualitative or both)
57
what is the dominant clincial manifestation of von willebrand disease
Mucocutaneous bleeding
58
what is the factor VIII complex made of
VonWillebrand factor
| Factor VIII procoagulant
59
are vWF and factor VIII made by the same gene
No, but different genes on the same chromosome
60
what does vWF do
carrier molecule for factor VIII
| glue between damaged endothelium and platelets (primary hemostasis)
61
when is factor VIII procoagulant released for associated with vWF
when a clot is formed
62
what does Factor VIII do once release from vWF
participated in the generation of factor X(secondary hemostasis)
63
where is factor VIII synth and vWF synth
Factor VIII in liver
| vWF in endothelial cells
64
how mant people are affected by von willebrand disease
less than 1% (the most common inherited bleeding disorder
65
when do symtoms of von willebrand disease improve
after adolescence
66
what is the most common of von Willebrand disease types
most common: decreased vWK
67
what does a decrease in vWK do to factor VIII
decreases the level of it in the blood
68
what type of von willebrand disease is autosomal recessive
Type III (total absence)
69
what are the laboratory manifestations of Von Wilebrand disease
prolonged bleeding time
Prolonged PTT(due to decreased Factor VIII)
Decreased vWF
Decreased factor VIII
70
what do platelet studies show during von willebrnad disease
abnormal in 1/3
71
what therapies can be used in von willebrand disease
desmopressin (releases vWF from endothelial cells)
antibrinolytic agents in mild cases
factor VIII concentrates containing vWF and cryoprecipitate in more sereve cases
72
hows is hemophilia A transmitted
X-linked recessive
73
what causes hemophilia A
deficiency of factor VIII
74
what happens when you have hemophilia A
recurrent soft tissue bleeding
75
when do symptoms of hemophilia A start
early childhood
76
clinical manifestation of hemophilia A
```
hemarthrosis
Soft tissue bleeding
excessive bleeding with trauma
intramuscular hematomas
intracerebral hemorrhage
bleeding into other tissues
```
77
Lab results of Hemophilia A (BT/PFA-100, PTT, Factor VIII, vWF:Ag, vWF:Rcof, Factor IX)
```
BT/PFA-100: normal
PTT: prolonged
Factor VIII: decreased
vWF:Ag: normal
vWF:RCof: normal
Factor IX: normal
```
78
how much factor VIII is there in severe hemophilia A
less than 1 percent
79
what happens in severe hemophilia A
recurrent spontaneous soft tissue and joint space bleeding (hemarthrosis)
80
how much factor VIII is there in moderate Hemophilia A
1-5% factor VIII
81
what happens in moderate hemophilia A
bleeding with minor trauma
82
how much factor VIII is there in mild Hemophilia A
greater than 5% Factor VIII
83
what happens in mild hemophilia A
bleeding with major trauma
84
how does one treat hemophilia A
factor VIII concentrates
Recombinant Factor VIII
Inhibitors of fibrinolysis
85
what are the disease related Hemophilia A complications
Arthritis and joint destruction
Pseudotumors
Intracranial bleeding
Retroperitoneal bleeding
86
what are the treatment related complications
antibodies to Factor VIII
infectious diseases
hemolysis
allergic reaction
87
what is the most common hereditary cause for serious bleeding
Hemophilia A
88
how is hemophilia B transmitted
Sex linked recessive disorder
89
what causes hemophilia B
deficiency of factor IX
90
what are the clinical presentation of hemophilia B
similar to Hemophilia A
91
what are the laboratory presentation of Hemophilia B
similar to hemophilia A
92
what are the classifications of mehophilia B
mild
moderate
Severe
93
what case of hemophilia can be difficult yo recognize clinically
Mild Hemophilia B
94
what are the disease related complications of hemophilia B
arthritis and joint destruction
pseudotumors
intracranial bleeding
retroperitoneal bleeding
95
what are the treatment related complications of hemophilia B
antibodies to factor IX
| Infectious diseases
96
how can one treat hemophilia B
factor IX concetrates
Recombo Factor IX
Inhibitors of fibrinolysis
97
what causes thrombocytopenia
decreased platelet production
98
what is the mechanisms of thrombocytopenia
increased destruction
decreased production
sequesttration
99
how can evaluate thrombocytopenia
```
- Clinical history/setting of
prolonged bleeding or hemorrhage (petechial)
- peripheral blood smear
- Bone marrow examination
- Platelet autoantibody determination
```
100
what is the platelet count for thrombocytopenai
less than 100,000 per microleter
101
when does spontaneous bleeding occur for thrombocytopenia
below 20,000
102
how does bleeding due to thrombocytopenia appear
petechial hemorrhages in skin and muccous membranes
103
what causes immune thrombocytopenia Purpura
immune mediated destruction of platelets by autoantibodies directed at the platelet membrane antigens
104
what is the target for immune thrombocytopenic Purpura(ITP)
GPIb/IX and IIb/IIIa
105
what happens to the platelets that are coated with
sequested in the speel and reticuloendothelial system
106
when does Acute and chronic immune thrombocytopenic purpura form
acute: childhood
chronic: adult
107
what follows acute immune thrombocytopenic Purpura
Viral prodrome and severe thrombocytopenia
108
what follows chronic immune thrombocytopenia Purpura
no antecedent infection
109
how does acute and chronic ITP come on
acute is sudden
| Chronic is gradual
110
how severe is acute and chronic Immune thrombocytopenic purpura
acute has severe thrombocytopenia
| chronic is moderate thrombocytopenia
111
does acute and chronic ITP remiss on its own
Acute: frequently undergoes spontaneous remission
Chronic: infrequent spontaneous remission
112
M/F ratio of acute and chronic ITP
Acute: M/F is 1 to 1
chronic: more females
113
what are the clinical features of ITP
petchial hemorrhages
Gingival bleeding
Ecchymoses (bruising)
bleeding with trauma or surgery
114
what happens to Megakaryocytes in ITP
normal to increased
115
microangiopathic changes on a blood smear for ITP
No changes
116
how does one treat ITP
corticosteroids
Intravenous immunoglobulin
Immunosuppression
Splenectomy
117
what is thrombotic thrombocytopenic purpura
acute disorder characterized by intravascular platelet activation with formation of plaetelet-rich microthrombi throughout the circulation
118
what causes thrombotic thrombocytopenic purpura
deficiency of ADAMTS 13
119
what is ADAMTS 13
metalloproteinase that normally degrade very high molecular weight vWF
120
how is thrombotic thrombocytopenic purpura transmitted
inherited or acquired
121
what happens if thrombotic thrombocytopenic purpura is leaf untreated
High mortality
122
what is disseminated inctravascular coagulation
Unregulated, widespread intravascular activation of the hemostatic system
123
what happens in disseminated intravascular coagulation
- Systemic formation of thrombin and plasmin with simultaenous microthrombi formation
- consumption of clotting factors that promote bleeding
124
what are the clinical settings for DIC
Infections(gram negative sepsis)
tissue injury (trauma, burn, surgery)
obstetrical complications
Certain malignancies
125
clinical manifestations of DIC
```
bleeding from multiple sites
Thromboembolic problems
Hypotension and shock
Respiratory dysfunction
Hepatic dysfunction
Renal dysfunction
CNS dysfunction
```
126
how to treat DIC
remove/reverse initaiting stimulus
| Supportive therapy with transfusions of blood products(FFP, Cryoprecipiatates, Platelets)
127
what is FFP
coagulation and regulatory proteins
128
what are Cryoprecipitates
fibrinogen
VIII
vWF
