Coagulation and platelet Flashcards
1
Q
normal hemostasis is a Precisely orchestrated process involving ___________________ that occur at the site of vascular injury and
culminates in the formation of blood clot, which
serves to prevent or limit the extent of bleeding.
A
platelets, clotting factors, and endothelium
2
Q
STEPS IN HEMOSTASIS
A
ARTERIOLAR VASOCONSTRICTION
PRIMARY HEMOSTASIS
SECONDARY HEMOSTASIS
CLOT STABILIZATION AND RESORPTION
3
Q
Occurs immediately and markedly reduces blood
flow to the injured area
A
ARTERIOLAR VASOCONSTRICTION
4
Q
Reflex neurogenic mechanism
A
ARTERIOLAR VASOCONSTRICTION
5
Q
Disruption of endothelium exposes _____ and _____,
which promote platelet adherence and activation, this is beginning of primary hemostasis
A
vWF and collagen
6
Q
Activation of platelet results in
A
dramatic shape
change as well as release of secretory granules
7
Q
Within a few minutes, the secreted products
recruit additional platelets that undergo
aggregation to form a primary hemostatic plug
A
primary hemostasis
8
Q
Vascular injury exposes tissue factors at the site
of injury
Tissue factors binds and activates factor VII,
setting in motion a cascade of reactions that
culminates in thrombin generation.
A
SECONDARY HEMOSTASIS
9
Q
cleaves fibrinogen into insoluble fibrin
and activates platelets (2ndary)
A
thrombin
10
Q
consolidates the initial platelet plug
A
secondary hemostasis
11
Q
Polymerized fibrin and platelet aggregates
undergo contraction to form a solid, permanent
plug
A
CLOT STABILIZATION AND RESORPTION
12
Q
At this stage, counter-regulatory mechanisms (tPA) are set into motion that limit clotting to the site
of injury and eventually lead to clot resorption and
tissue repair.
A
CLOT STABILIZATION AND RESORPTION
13
Q
Excessive bleeding can result from:
A
- Increased fragility of vessels
- Platelet deficiency or dysfunction
- Derangement of coagulation, alone or in
combination
14
Q
The normal hemostatic response involves the
A
blood vessel wall, the platelets, and the
clotting cascade
15
Q
Assesses the extrinsic and common coagulation
pathways (factors VII, X, V, II [prothrombin], and
fibrinogen)
A
PROTHROMBIN TIME (PT) 7,10,5,2
16
Q
Prolonged PT can result from deficiency or
dysfunction of
A
factor V, factor VII, factor X, prothrombin, or fibrinogen
17
Q
Assesses the intrinsic and common clotting
pathways (factors XII, XI, IX, VIII, X, V, II, and
fibrinogen)
A
PARTIAL THROMBOPLASTIN TIME (PTT)
12, 11, 10, 9, 8, 5, 2
18
Q
fibrinogen)
Prolongation of the PTT can be due to deficiency
or dysfunction of factors
A
V, VIII, IX, X, XI, or XII,
prothrombin, or fibrinogen, or to interfering
antiphospholipid antibodies
19
Q
platelet reference range
A
150x10^3 to 350x10^3
platelets/uL
20
Q
platelet High counts may be indicative of a
A
myeloproliferative neoplasm, but are more likely
to reflect reactive processes that increases platelet production
21
Q
T or F
No single test provides an adequate assessment
of the complex function of platelet
A
T
22
Q
Test of platelet fx
A
Tests of platelet aggregation
Quantitative and qualitative test of von Willebrand factor
Bleeding time-
23
Q
infections which Often induce petechial and purpuric hemorrhages
A
meningococcemia, other forms of septicemia infective endocarditis and several of the rickettsioses
24
Q
Infection induced petechial and purpuric hemorrhage mechanism
A
Microbial
damage to the microvascular (vasculitis) and disseminated intravascular coagulation
25
vascular injury is mediated by the deposition of drug
induced immune complexes in vessel walls,
leading to
hypersensitivity (leukocytoclastic)
| vasculitis
26
Associated with microvasculature bleeding due to
| collagen defects that weaken vessel walls.
SCURVY AND THE EHLERS-DANLOS SYNDROME
27
HENOCH-SCHONLEIN PURPURA is Systemic immune disorder characterized by
purpura, colicky abdominal pain, polyarthralgia, and acute
| glomerulonephritis
28
result from the deposition of circulating immune complexes within vessels
throughout the body and within the glomerular
mesangial regions
HENOCH-SCHONLEIN PURPURA
29
Autosomal dominant disorder that can be caused by mutations in at least five different genes, most of which modulate TGF-B Signaling
HEREDITARY HEMORRHAGIC
| TELANGIECTASIA (WEBER OSLER-RENDU SYNDROME
30
Dilated , tortuous blood vessels with thin walls
| that bleed readily
HEREDITARY HEMORRHAGIC
| TELANGIECTASIA (WEBER OSLER-RENDU SYNDROME
31
in HEREDITARY HEMORRHAGIC
TELANGIECTASIA (WEBER OSLER-RENDU SYNDROME, Bleeding can occur anywhere , but it is most
common
under the mucous membranes of the
nose (epitaxis), tongue, mouth,and eyes and
through gastrointestinal tract
32
Weaken blood vessel walls and cause bleeding
This complication is most common with amyloid light chain (AL) amyloidosis and often manifests as mucocutaneous petechiae.
PERIVASCULAR AMYLOIDOSIS
33
Among these conditions, serious bleeding is most
| often associated with
HEREDITARY HEMORRHAGIC
| TELANGIECTASIA (WEBER OSLER-RENDU SYNDROME
34
Bleeding disorders due to vessel wall abnormalities
```
Infections
Drug Rxns
Scurvy and the ehlers-danlos syndrome
Henoch-schonlein pupura
HEREDITARY HEMORRHAGIC
TELANGIECTASIA (WEBER OSLER-RENDU SYNDROME
PERIVASCULAR AMYLOIDOSIS
```
35
Count less than________ is generally
| considered to constitute thrombocytopenia.
150,000 platelets /ul
36
can aggrevate
| posttraumatic bleeding.
20,000 to 50000 platelets/ul
37
When thrombocytopenia is isolated, the PT and
| PTT are
normal
38
causes of thrombocytopenia
Decreased platelet production
Decreased platelet survival
Sequestration
Dilution
39
`causes decreased platelet production
```
Conditions that depress marrow output
generally or affect megakaryocytes
selectively.
Certain drugs and alcohol
HIV, which may infect megakaryocytes and
inhibit platelet production.
Myelodysplastic syndrome.
```
40
is caused by the
| deposition of antibodies or immune complexes on platelets
Immune thrombocytopenia
41
non immunologic causes of thrombocytopenia
o Disseminated intravascular coagulation
(DIC) and the thrombotic microangiopathies.
o Mechanical injury such as individuals with
prosthetic heart valves
42
platelet _____ can rise to 80% to 90% when the spleen is
enlarged , producing moderate degress of
thrombocytopenia
Sequestration
43
Massive transfusions can produce dilutional
| thrombocytopenia.
Dilution
44
Autoantibody mediated destruction of platelets
It can occur in the setting of a variety of predisposing
conditions and exposures(secondary) or in the
absence of any known risk factors( primary or
idiopathic)
CHRONIC IMMUNE THROMBOCYTOPENIC PURPURA
45
CITP pathogenesis
Auto-antibodies , against glycoproteins IIb-IIIa or Ib-IX , can be demonstrated in the plasma and
bound to the platelet surface in about 80% of the
patients
46
CITP spleen morphology
normal size.
congestion of the sinusoids
enlargement of the splenic follicles
often associated with prominent reactive germinal centers.
47
CITP marrow morphology
modestly increased
number of megakaryocytes. Some are apparently
immature with large, non-lobulated , single nuclei.
48
CITP peripheral blood morphology
abnormally
| large platelets.
49
CITP female to male ratio
3:1
50
Pinpoint hemorrhages (petechiae) are especially
prominent in the dependent areas where the
capillary pressure is
higher
51
Typical laboratory findings (CITP)
o Low platelet count
o Normal or increased megakaryocytes in the
bone marrow and large platelets in the
peripheral blood
o PT and PTT are normal
o Tests for platelet autoantibodies suffer from
low sensitivity and specificity and are not
clinically useful.
o Therefore, the diagnosis is one of the
exclusion and can be made only after other
causes of thrombocytopenia have been ruled
out
52
CITP treatment
```
Respond to glucocorticoids
Splenectomy (severe thrombocytopenia)
Immunomodulatory agents such as IV
immunoglobulin or anti-CD20 antibody
(rituximab) are often effective
```
53
T or F
AITP is Mainly a disease of childhood occurring with
equal frequency in both sexes.
T
54
AITP symptoms occur
Often 1 to 2 weeks after a self-limited
| viral illness
55
AITP is usually resolved within
6 months
56
drugs most commonly implicated in DIT
quinine (anti-malarial), quinidine (antiarrhythmic), and vancomycin (antibiotic)
57
Thrombocytopenia, which may be severe, can
| occur in those who are taking
platelet inhibitory
drugs that bind glycoprotein IIb/IIIa (ex.
abciximab, tirofiban)
58
Thrombocytopenia occurs in about 5% of persons
| receiving heparin and is of two types:
o Type I HIT
| o Type II HIT
59
```
Occurs rapidly after the onset of
therapy and is of little clinical
importance, sometimes
resolving despite the
continuation of therapy.
```
o Type I HIT
60
It most likely results from a direct platelet-aggregating effect of heparin.
o Type I HIT
61
Occurs 5 to 14 days after therapy begins (or sooner if the person has been sensitized to heparin)
and, paradoxically, often leads to venous and arterial thrombosis.
o Type II HIT
62
Caused by antibodies that
| recognize complexes of heparin and platelet factor 4, a normal component of platelet granules.
o Type II HIT
63
receptor and co-receptor,
respectively, for HIV, are found on megakaryocytes, allowing these cells to be
infected
CD4 and CXCR4
64
HIV-infected megakaryocytes are prone to
apoptosis
65
HIV infection also causes B-cell
hyperplasia and
| dysregulation
66
THROMBOTIC MICROANGIOPATHIES
TTP & HUS
67
Clinical syndromes that are caused by insults that
lead to excessive activation of platelets, which deposit
as thrombi in small blood vessels
THROMBOTIC MICROANGIOPATHIES
68
Defined as the pentad of fever,
thrombocytopenia, microangiopathic
hemolytic anemia, transient neurologic
deficits, and renal failure.
THROMBOTIC THROMBOCYTOPENIC PURPURA
| TTP
69
Also is associated with microangiopathic
hemolytic anemia and thrombocytopenia but
is distinguished by the absence of
neurologic symptoms, the prominence of
acute renal failure, and its frequent
occurrence in children.
HEMOLYTIC UREMIC SYNDROME (HUS)
70
THROMBOTIC THROMBOCYTOPENIC PURPURA
| Caused by a deficiency in a plasma enzyme called
ADAMTS13, also designated “vWF metalloprotease.”
71
ADAMTS13 degrades
very high-molecular-weight multimers of vWF
72
T or F
In its absence (ADAMTS13), large multimers accumulate in plasma
and tend to promote spontaneous platelet activation
and aggregation.
T
73
- an autoantibody that inhibits the
metalloprotease activity of ADAMTS13 is
present.
Acquired
74
the onset is often delayed until adolescence, and the symptoms are episodic.
Thus, factors other than ADAMTS13 deficiency (e.g., a superimposed
vascular injury or prothrombotic
state) must be involved in triggering
full-blown TTP.
Hereditary
75
removes
autoantibodies and provides functional ADAMTS13,
TTP (which once was uniformly fatal) can be treated successfully in more than 80% of patients
plasma exchange
76
Strongly associated with infectious
gastroenteritis caused by Escherichia coli
strain O157:H7, which elaborates a Shigalike toxin.
“Typical” HUS
77
Defects in complement factor H, membrane
cofactor protein (CD46), or factor I, proteins
that act to prevent excessive activation of the
alternative complement pathway.
“Atypical” HUS
78
BLEEDING RELATED TO REDUCED PLATELET
| NUMBER: THROMBOCYTOPENIA
CHRONIC IMMUNE THROMBOCYTOPENIC PURPURA
ACUTE IMMUNE THROMBOCYTOPENIC PURPURA
DRUG-INDUCED THROMBOCYTOPENIA
HEPARIN-INDUCED THROMBOCYTOPENIA
HIV-ASSOCIATED THROMBOCYTOPENIA
THROMBOTIC MICROANGIOPATHIES: TTP & HUS
THROMBOTIC THROMBOCYTOPENIC PURPURA
HEMOLYTIC UREMIC SYNDROME (HUS)
79
BLEEDING DISORDERS RELATED TO DEFECTIVE
| PLATELET FUNCTION
BERNARD-SOULIER SYNDROME
GLANZMANN THROMBASTHENIA
STORAGE POOL DISORDERS
INGESTION OF ASPIRIN AND OTHER NSAID
80
Inherited disorders of platelet function can be
| classified into three pathogenically distinct groups:
1. Defects of adhesion
2. Defects of aggregation
3. Defects of platelet secretion (release reaction)
81
Defective adhesion of platelets to subendothelial
| matrix
BERNARD-SOULIER SYNDROME
82
BERNARD-SOULIER SYNDROME
is an Inherited deficiency of the platelet membrane
glycoprotein complex
Ib-IX
83
This glycoprotein is a receptor for vWF and is
essential for normal platelet adhesion to the
subendothelial extracellular matrix
glycoprotein complex Ib-IX
84
bernard soulier syndrome clinical manifestations:
variable, often severe,
| bleeding tendency.
85
Bleeding due to defective platelet aggregation
GLANZMANN THROMBASTHENIA
86
GLANZMANN THROMBASTHENIA
- Platelets fail to aggregate in response to ADP,
collagen, epinephrine, or thrombin because of
deficiency or dysfunction of
glycoprotein IIb-IIIa
87
Characterized by the defective release of certain
mediators of platelet activation, such as
thromboxanes and granule-bound ADP.
STORAGE POOL DISORDERS
88
s a potent, irreversible inhibitor of
cyclooxygenase, an enzyme that is required for the
synthesis of thromboxane A2 and prostaglandins.
aspirin
89
BLEEDING DISORDERS RELATED TO
| ABNORMALITIES IN CLOTTING FACTORS
```
HEREDITARY DEFICIENCIES
ACQUIRED DEFICIENCIES
FACTOR VIII-vWF COMPLEX
VON WILLEBRAND DISEASE
HEMOPHILIA A (FACTOR VIII DEFICIENCY)
HEMOPHILIA B (CHRISTMAS DISEASE, FACTOR IX
DEFICIENCY)
DISSEMINATED INTRAVASCULAR COAGULATION (DIC)
```
90
Bleeding due to coagulation factor deficiencies
| commonly manifest as
large posttraumatic
ecchymoses or hematomas, or prolonged bleeding
from a laceration or after a surgical procedure
91
The most common and important inherited
| deficiencies of coagulation factors affect
factor 8
| hemophilia A) and factor 9 (hemophilia B
92
Vitamin K deficiency impairs the synthesis of
factors II, VII, IX, X and protein C
93
All coagulation factors are produced in the liver
except____ which is produced by endothelial
cells.
factor VIII (8)
94
are caused by qualitative or quantitative defects
hemophilia A and von Willebrand disease
95
aids F IX in activation of F X.
F VIII-VWF
96
o Essential cofactor of factor IX, which converts F
X to FXa
o Binds to and is stabilized by vWF, an interaction
that increases the half-life of F VIII from about
2.4 hours to about 12 hours.
Factor VIII
97
o Secreted into the circulation by endothelial cells
| o Function in stabilization of FVIII
vWF
98
promote adhesion of platelets to the
| subendothelial matrix
vWF
99
vWF also may promote platelet aggregation by
| binding to activated
GpIIb/IIIa integrins
100
vWF function is assessed using the
Ristocetin
| agglutination test
101
```
The most common symptoms:
Spontaneous bleeding from mucous
membranes (e.g. epistaxis), excessive
bleeding from wounds, menorrhagia
It is usually transmitted as an autosomal
dominant disorder
```
VON WILLEBRAND DISEASE
102
AD (autosomal dominant) disorder characterized by a mild to moderate vWF
deficiency
Type 1 and Type 3 von Willebrand disease
103
– is associated with a spectrum of
mutations, including point substitutions
that interfere with maturation of the vWF
protein or that result in rapid clearance
from plasma; this disorder is mild; there
is still production of vWF
type 1 vWF disease
104
```
disease is an autosomal
disorder usually caused by deletions or
frameshift mutations involving both
alleles, resulting in little to no vWF
synthesis; mutations here are bigger,
more severe
```
type 3vWF disease
105
the most common subtype in type 2 VWF disease
2a
106
vWF is expressed in normal amounts, but missense mutations are present that
lead to defective multimer
assembly.
Type 2 von Willebrand disease
107
accounts for 25% of all cases and is associated
| with mild to moderate bleeding.
Type 2 von Willebrand disease
108
T or F
Type 2 vWF is Associated with a prolonged PTT
T (intrinsic)
109
Type 1 or 2 vWF tx
can be treated with
desmopressin as a prophylactic
measure, or infusions of plasma concentrates containing factor VIll and
vWF, or with recombinant vWF.
110
```
must be treated
prophylactically with plasma
concentrates and factor VIll infusions to
prevent severe "hemophilia-like"
bleeding.
```
Type 3 disease
111
Most common hereditary disease associated with
| life-threatening bleeding
HEMOPHILIA A (FACTOR VIII DEFICIENCY)
112
is inherited as an X-linked
recessive trait and thus affects mainly males and
homozygous females.
Hemophilia A
113
Most severe deficiencies result from an
inversion involving the X chromosome that
| completely abolishes the synthesis of factor VIll.
114
T or F
| In Factor VIII deficiency, Petechia are characteristically absent
T
115
Hemophilia a TREATMENT
Infusions of recombinant factor VIll.
Recently, bispecific antibodies have been
developed that bind factor IXa to factor X;
these antibodies bypass the need for factor
VIll and are particularly effective in patients
with factor VIII antibody inhibitors
116
A wide spectrum of mutations involving the gene that
| encodes factor IX is found in
hemophilia B
117
T or F
| Hemophilia B is X-linked recessive trait like hemophilia A
T
118
Hemophilia b Diagnosis is possible only by
assay of the factor
levels, that’s the only way to differentiate them, you
have to assay or do a mixing studies between factor
8 and 9 but clinically they are the same
119
T or F
In hemophilia B, PTT is prolonged and PT is normal
T
