CHAPTER 1 - HEMOSTASIS PART 6 Flashcards
1
Q
From an external substance
A
ACQUIRED DEFECTS OF PLATELET FUNCTION
2
Q
- Drug-related
A
• Aspirin
• NSAIDs and other COX-2 inhibitors (naproxen and ibuprofen)
• Other Antiplatelet medications: ticlopidine and clopidogrel
• Dextran
3
Q
acytelate the cyclooxygenase enzyme
A
Aspirin
4
Q
adding/removin one cpd to make it nonfuncitonal
A
acytelate
5
Q
– secretes thromboxane and prostaglandin
A
cyclooxygenase enzyme
6
Q
(stimulates the activation of plt and aggregation)
A
thromboxane and prostaglandin
7
Q
blood donation: deferral after 14 days; plasma and plt are nonfuncitonal
A
NSAIDs and other COX-2 inhibitors (naproxen and ibuprofen)
8
Q
.Prevent blood clotting by preventing plt aggregation
A
ticlopidine and clopidogrel
9
Q
Administered to enhance fibrinolysis (plt clot – stabilization of coagulation – agglutinates in the bv to arrest bleeding – interacts w/ bf = not healthy)
A
Dextran
10
Q
Side effect: reduce plt adhesion to vWF (interference to plt plug formation)
A
Dextran
11
Q
Normal:
A
140-450 x 109/uL
12
Q
: transient thrombocytopenia
A
100-150 x 109/uL
13
Q
(due to medication but can go back as soon as it is eliminated)
A
: transient thrombocytopenia
14
Q
- abnormally low
A
• ≤ 100,000/ pL
15
Q
- bleeding possible
A
• 30,000-50,000/ pL
16
Q
- spontaneous bleeding
A
• ≤ 30,000
17
Q
- severe spontaneous bleeding
A
• ≤ 5,000/pL
18
Q
-decrease in circulating platelets
A
THROMBOCYTOPENIA
19
Q
-less than 100,000/uL
A
THROMBOCYTOPENIA
20
Q
-increase in circulating platelets
A
THROMBOYTOSIS /THROMBOCYTHEMIA
21
Q
-more than 450,000/uL
A
THROMBOYTOSIS /THROMBOCYTHEMIA
22
Q
-bleeding -
A
THROMBOCYTOPENIA
23
Q
hallmark for myeloproliferative diseases
A
Primary Thrombocytosis
24
Q
- polycythemia vera: thrombocytosis is in sync w/ an abnormality of the rbc
A
THROMBOYTOSIS /THROMBOCYTHEMIA
25
THROMBOCYTOPENIA
1. Decreased production
2. Blood Transfusion
3. Increased Destruction or Consumption
26
1. Decreased production
a. Megakaryocyte hypoproliferation
b. Ineffective thrombopoiesis
c. Marrow replacement (infiltration) by abnormal cells
27
a. Megakaryocyte hypoproliferation
a.1) Inherited/Congenital Hypoplasia
a.2) Acquired/Drug induced Hypoplasia
28
Inherited/Congenital Hypoplasia:
1. May Hegglin Anomaly
2. TAR Syndrome
3. Fanconi Anemia
4. Neonatal Thrombocytopenia
5. Bernard Soulier Syndrome
6. Wiskott Aldrich
29
-Large plt (20 um); dohle like bodies (neutrophils, monocytes)
May Hegglin Anomaly
30
-Mutation in MYH9 gene
May Hegglin Anomaly
31
Encodes for myosin heavy chain
May Hegglin Anomaly
32
– contractile protein in plt (imp for activation)
Thrombostenin
33
Causing thrombocytopenia (abnormally large plt but low in level)
May Hegglin Anomaly
34
-absence/hypoplasia of radial bones (small arm)
TAR Syndrome
35
-Mutation in RBM8A gene
TAR Syndrome
36
-occurs in neonates
Fanconi Anemia
37
-bone and visceral organ abnormalities
Fanconi Anemia
38
-pancytopenia (decrease in all blood cells)
Fanconi Anemia
39
-onset: w/in 72 hours of birth
Neonatal Thrombocytopenia
40
- associated with infections with TORCH
Neonatal Thrombocytopenia
41
Toxoplasma, Rubella, CMV, HIV, Herpes
Neonatal Thrombocytopenia
42
-small platelets
Neonatal Thrombocytopenia
43
-absence of megakaryocytes
Neonatal Thrombocytopenia
44
: directly affect the fetal BM megakaryocyte
chlorthiazide and tolbutamide
45
-Large plt but few
5. Bernard Soulier Syndrome
46
-Dense granules; small platelets
6. Wiskott Aldrich
47
-suppresses BM megakaryocyte production and other cells.
Acquired/Drug induced Hypoplasia
48
Acquired/Drug induced Hypoplasia Examples:
-methotrexate, busulfan, cytosine, arabinoside, cyclosphamide, cisplatin
49
– assoc. w/ specific gene chromosomal abnormality
Inherited/Congenital Hypoplasia
50
: HIV treatment
-Zidovudine
51
side effect – severe thrombocytopenia
-Zidovudine
52
eliminates infection but negatively affects the healthy cells
-Zidovudine
53
: thrombocytosis treatment
-Anagrelide
54
(eliminating some platelet to go back to normal level by increasing sequestration or affecting the life span of plt)
-Anagrelide
55
improper administration causes thrombocytopenia
-Anagrelide
56
: long-term consumption may lead to thrombocytopenia
-Ethanol
57
bleeding may not be arrested easily
-Ethanol
58
: after chemotherapy, there will be pancytopenia, destroying some healthy cells
-Recombinant IL-2
59
restores platelet
-Recombinant IL-2
60
chemotherapy-induced thrombocytopenia treatment
-Recombinant IL-2
61
• Seen in megaloblastic anemias
Ineffective thrombopoiesis
62
Pernicious anemia, Folic acid deficiency and Vitamin B 12 deficiency
Ineffective thrombopoiesis
63
: affects maturation stage of cell; immature cells remained large; nucleus continue to divide but the cytoplasm will not; main cause
Folic acid deficiency and Vitamin B 12 deficiency
64
: response will follow after 1-2 weeks
Vitamin replacement
65
-impaired DNA synthesis = BM produce abnormal megakaryocytes
Ineffective thrombopoiesis
66
-Platelets: decreased survival time and abnormal function
Ineffective thrombopoiesis
67
-abnormality in the division and maturation of the megakaryocyte – even plt shedding is affected (ineffective)
Ineffective thrombopoiesis
68
-due to infiltration of abnormal cells, inhibitors of thromobopoiesis are produced contributing to thrombocytopenia
Marrow replacement (infiltration) by abnormal cells
69
Suppression of normal cell/megakaryocyte production - Affecting thrombopoiesis
Marrow replacement (infiltration) by abnormal cells
70
-inhibits maturation of the megakaryocyte
Marrow replacement (infiltration) by abnormal cells
71
: lost of platelet containing blood products and coagulation
factors
• Donor
72
: may have alloantibodies directed against the antigens of blood products
• Recipient
73
: dilution of px platelet
• Recipient
74
3. Increased Destruction or Consumption
a. non-immune (premature activation & consumption)
b. Immune destruction
75
a. non-immune (premature activation & consumption)
Thrombotic Thrombocytopenic Purpura (TTP)
DIC
HUS
Infections (eg. Dengue)
76
Secondary
non-immune (premature activation & consumption)
77
caused by mechanical trauma
non-immune (premature activation & consumption)
78
due to inflammation, infection, or gene mutation
non-immune (premature activation & consumption)
79
does not involve the immune system
non-immune (premature activation & consumption)
80
Gene that produces enzyme, which controls the VWF
(ADAMTS-13)
81
responsible for cutting VWF to interact w/ plt in a normal size
(ADAMTS-13)
82
- has uncontrolled and very large VWF
Thrombotic Thrombocytopenic Purpura (TTP)
83
VWF is unfolded, multimer, and hyper adhesive (creating a thrombus)
Thrombotic Thrombocytopenic Purpura (TTP)
84
: composed of 1 VWF + plt
- Hyaline thrombi
85
- thrombocytopenia: circulating plt decreases due to thrombi formation
Thrombotic Thrombocytopenic Purpura (TTP)
86
- aka Moschcowitz Symdrome
Thrombotic Thrombocytopenic Purpura (TTP)
87
- thrombocytopenia: due to simultaneous coagulation
Disseminated Intravascular Coagulation (DIC)
88
: composed of fibrinogen + plt (plt is trapped in agglutination during coagulation concerning fibrinogen)
- DIC thrombi
89
: invasive bacteria in the colon that destroys mucosa lining
- S.dysentiriae/E.coli 0157:H7 serotype
90
- thrombocytopenia: as soon as the colon is damaged, the endothelium of the colon releases VWF creating thrombi that may go to the renal structure
Hemolytic Uremic Syndrome (HUS)
91
Involves the immune system, Abs, and auto-Abs
b. Immune destruction
92
- Acute: onset after 1-3 weeks
Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
93
Ab and Ag forms an immune complex that binds w/ plt = elimination of Gp IIb-IIIa
Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
94
-after plt is destroyed, it will be removed by the reticuloendothelial cells from the circulation
Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
95
- unfractioned heparin administration: destroys PF4, affecting aggregation and plt destruction
Heparin-Induced Thrombocytopenia
96
: used to test platelet aggregation
- Ristocetin
97
in vivo/unfractioned form administration will facilitate interaction of VWF + Gp Ib-IX causing adhesion, aggregation, and in vivo agglutination
- Ristocetin
98
: can cause transient tmrombocytopenia
- Hematin
99
: induces thrombocytopenia
- Rotamine sulfate (for parasitic infection) and Bleomycin ( for bacterial infection)
100
Deficiency: disintegrase + ADAMTS-13
TTP
101
-platelets are trapped in fibrin clots
DIC
102
-VWF involvement
HUS
103
Disease triad: Microangiopathic Hemolytic Anemia, thrombocytopenia and neurologic abnormality
TTP
104
onset with platelet consumption, factor V,VIII and fibrinogen reduced level
-acute DIC
105
Due to S.dysentiriae/E.coli 0157:H7 serotype
HUS
106
Onset on children
HUS
107
Life threatening
DIC
108
Characterized by: erosive damage to the colon + bloody diarrhea
HUS
109
-no apparent cause
ITP
110
-presence of anti-platelet ab (IgG)
ITP
111
-develops IgG antibody specific for heparin plt factor 4 complex
HIT
112
-due to unfractioned heparin administration
HIT
113
abrupt onset, usually on children
Acute: ITP
114
mumps, chicken pox, small pox, and measles
ITP
115
Characterized by bruising, petechiae and epistaxis
ITP
116
Drugs affecting thrombocytopenia:
- Ristocetin
- Hematin
- Rotamine sulfate
- Bleomycin
HIT
117
: any age onset
Chronic ITP
118
rubella, chicken pox, ruboela
ITP
119
Characterized by: menorrhagia, epistaxis and bruising
ITP
120
Splenic sequestration Seen in:
hypersplenism/splenomegaly
121
(Gaucher’s, Hodgkin, Cirrhosis, Sarcoidosis, Lymphoma)
hypersplenism
122
more plt can be sequestered, reducing the circulating plt (thrombocytopenia)
hypersplenism
123
– removal of the spleen = low plt (thrombocytopenia)
splenomegaly
124
THROMBOYTOSIS/THROMBOCYTHEMIA
1. Primary Thrombocytosis
2. Secondary/Reactive Thrombocytosis
125
-hallmark of myeloproliferative disorders
Primary Thrombocytosis
126
-unregulated plt production
Primary Thrombocytosis
127
-variable size (small and large) affecting function
Primary Thrombocytosis
128
-increased megakaryocyte production in the bm
Primary Thrombocytosis
129
-myeloproliferative disorders: pcv, chronic myelogenous leukemia, myelofibrosis
Primary Thrombocytosis
130
plt can exceed up to 1 million/uL
Primary Thrombocytosis
131
-aka Essential Thrombocytopenia
Primary Thrombocytosis
132
-does not exceed 800,000/uL
Secondary/Reactive Thrombocytosis
133
-secondary to inflammation and trauma
Secondary/Reactive Thrombocytosis
134
-occurs to compensate for the lost platelet (betterment of the body)
Secondary/Reactive Thrombocytosis
135
-Ex. Childbirth, splenectomy, tissue necrosis, IDA
Secondary/Reactive Thrombocytosis
136
-exists for a short period of time
Secondary/Reactive Thrombocytosis
137
-normal plt morphologyand responds to normal stimuli
Secondary/Reactive Thrombocytosis
138
→ Excessive plasma proteins lead to hyperviscosity syndrome
Paraproteinemias (Multiple myeloma and Waldenstrom macroglobulinemia)
139
→ uremia: leads to decreased thromboxane synthesis, decreased adhesion, decreased platelet release, and decreased aggregation
Renal disease
140
May-Hegglin
Megakaryocyte hypoproliferation
141
in-utero exposure to certain drugs (particularly chlorothiazide diuretics and the oral hypoglycemic tolbutamide)
Neonatal Thrombocytopenia
142
• caused by a deficiency of a disintegrin an metalloproteinase with a thrombospondi type 1 motif, member 13 (ADAMTS-13).
TTP
143
involves the activation of both coagulation and fibrinolysis at the same time due to liberation of thromboplastic substance by damaged or abnormal cells
DIC
144
Associated with mild febrile illnesses, certain immunizations, and gastrointestinal disturbances
HUS
145
E. coli 0157:H7 or other Shiga/Vero toxin-producing bacteria
HUS
146
due to presence of anti-platelet antibodies of the IgG type
ITP
147
Most common in young females <15 y/o
ITP
148
patient develops IgG antibody specific for heparin-platelet factor 4 complexes
Heparin-Induced Thrombocytopenia
149
A. common side effect of unfractionated heparin administration
Heparin-Induced Thrombocytopenia
150
seen in myeloproliferative disorders
Primary Thrombocytosis
151
seen in splenic mobilization and in hemolytic anemias
Secondary/Reactive Thrombocytosis
152
(deformed with dumbbell shaped nuclei; could be reversed)
Ineffective thrombopoiesis
