3. Normal endothelium prevents thrombosis by
inhibiting platelet function. When vascular
endothelium injured these inhibitions overcome.
Platelets adhere through VWF.
PLATELET ADHESION leads to activation of GpIIb
IIIa receptor. Result in platelet aggregation.
Platelet plug is stabilised by fibrin mesh
4. Major regulator of platelet production –
thrombopoietin (TPO) is synthesized in ?
Harrison’s 18th Ed. 965
A. Kidney
B. Liver
C. Muscle
D. Adipose tissue
14. Drug induced thrombocytopenia usually resolves
how many days after drug withdrawal ?
Harrison’s 18th Ed. 967
A. 1 - 3 days
B. 3 - 7 days
C. 7 - 10 days
D. 14 - 21 days
15. Heparin-Induced Thrombocytopenia
Drug-induced thrombocytopenia due to heparin differs
from that seen with other drugs in two major ways.
(1) The thrombocytopenia is not usually severe, with nadir counts
rarely <20,000/L.
(2) Heparin-induced thrombocytopenia (HIT) is not associated
with bleeding and, in fact, markedly increases the risk of
thrombosis.
HIT results from antibody formation to a complex of
the platelet-specific protein platelet factor 4 (PF4) and
heparin.
The antiheparin/PF4 antibody can activate platelets
through the FcRIIa receptor and also activate
monocytes and endothelial cells.
16. HIT can occur after exposure to low-molecular-
weight heparin (LMWH) as well as unfractionated
heparin (UFH), although it is about 10 times more
common with the latter.
Most patients develop HIT after exposure to heparin
for 5–14 days.
17.
18. Laboratory Testing for HIT
HIT (anti-heparin/PF4) antibodies can be detected
using two types of assays. The most widely
available is an enzyme-linked immunoassay
(ELISA) with PF4/polyanion complex as the
antigen
The other assay is a platelet activation assay, which
measures the ability of the patient's serum to
activate platelets in the presence of heparin in a
concentration-dependent manner.
19. Treatment: Heparin-Induced Thrombocytopenia
discontinuation of heparin and use of alternative
anticoagulants.
The direct thrombin inhibitors (DTIs) argatroban and
lepirudin are effective in HIT.
The DTI bivalirudin and the antithrombin-binding
pentasaccharide fondaparinux are also effective but not
yet approved .
Danaparoid also can use
Warfarin therapy, if started, should be overlapped with a
DTI or fondaparinux, and started after resolution of the
thrombocytopenia and lessening of the prothrombotic
state.
20. Pseudothrombocytopenia is due to ?
Harrison’s 18th Ed. 965
A. Exercise
B. Laboratory artifact
C. Cold weather
D. Fasting
21. Pseudothrombocytopenia is most likely when blood
is collected with which of the following
anticoagulants ?
Harrison’s 18th Ed. 965
A. EDTA
B. Sodium citrate
C. Heparin
D. All of the above
22. IMMUNE THROMBOCYTOPENIC PURPURA
also termed idiopathic thrombocytopenic purpura
acquired disorder in which there is immune-
mediated destruction of platelets and possibly
inhibition of platelet release from the
megakaryocyte.
23. *Children are affected by an acute type of illness
following URT infection (usually viral).
* = incidence.♂ ♀
*Adults are affected by a more gradual onset of
disease with chronic course & without preceding
illness.
*Age < 40 years
* : = 3-4:1♀ ♂
24. ITP is termed secondary if it is associated with an
underlying disorder; autoimmune disorders,
particularly systemic lupus erythematosus (SLE),
and infections, such as HIV and hepatitis C, are
common causes.
25. Skin shows petechiae (pinpoint red hemorrhagic
spots) & ecchymoses.
Mucosal bleeding --- bleeding gum, epistaxis,
menorrhagia, metrorrhagia, GI bleeding &
hematuria
Intracranial hemorrhage is seen in 1%. Risk of
death 5%
No splenomegaly.
26. Laboratory Testing in ITP
Laboratory testing for antibodies (serologic testing)
is usually not helpful due to the low sensitivity and
specificity.
Bone marrow examination can be reserved for older
adults (usually >60 years) or those who have other
signs or laboratory abnormalities not explained by
ITP, or in patients who do not respond to initial
therapy. The peripheral blood smear may show large
platelets, with otherwise normal morphology.
Depending on the bleeding history, iron deficiency
anemia may be present
27. Laboratory testing is performed to evaluate for secondary
causes of ITP.
It should include testing for HIV infection and hepatitis C
(and other infections if indicated);
serologic testing for SLE, serum protein electrophoresis,
and immunoglobulin levels to potentially detect
hypogammaglobulinemia;
selective testing for IgA deficiency or monoclonal
gammopathies ,
if anemia is present, direct antiglobulin testing (Coombs
test) to rule out combined autoimmune hemolytic
anemia with ITP (Evans syndrome).
28. Treatment: Immune Thrombocytopenic Purpura
prednisone at 1 mg/kg usually
Rh0(D) immune globulin therapy (WinRho SDF), at
50–75 g/kg, is also being used in this setting.
Rh0(D) immune globulin must be used only in Rh-
positive patients.
Intravenous gamma globulin (IVIgG),
29. IVIgG has more efficacy than anti-Rh0(D) in
postsplenectomized patients. IVIgG is dosed at 2
g/kg total, given in divided doses over 2–5 days.
Rituximab, an anti-CD20 (B cell) antibody, has
shown efficacy in the treatment of refractory ITP.
Splenectomy has been used for treatment of patients
who relapse after glucocorticoids are tapered
30. Vaccination against encapsulated organisms
(especially pneumococcus, but also meningococcus
and Haemophilus influenzae, depending on patient
age and potential exposure) is recommended before
splenectomy
31. Thrombopoietin receptor agonists are now available
for the treatment of ITP.
Two agents, one administered subcutaneously
(romiplostim) and another orally (eltrombopag).
32. Evans’s syndrome refers to ? Harrison’s 18th Ed. 968
A. Autoimmune hemolytic anemia with ITP
B. SLE with ITP
C. HIV with ITP
D. Hepatitis C with ITP
33. Which of the following drugs is useful in refractory
ITP ? Harrison’s 18th Ed. 969
A. Rituximab
B. Romiplostim
C. Eltrombopag
D. All of the above
34. Inherited Thrombocytopenia
inherited in an autosomal dominant, autosomal
recessive, or X-linked pattern.
autosomal dominant thrombocytopenia are now
known to be associated with mutations in the
nonmuscle myosin heavy chain MYH9 gene.
Interestingly, these include the May-Hegglin
anomaly, and Sebastian, Epstein's, and Fechtner
syndromes, all of which have distinct distinguishing
features. A common feature of these disorders is
large platelets
35. Autosomal recessive disorders include congenital
amegakaryocytic thrombocytopenia,
thrombocytopenia with absent radii, and Bernard
Soulier syndrome. The latter is primarily a functional
platelet disorder due to absence of GPIb-IX-V, the
VWF adhesion receptor.
36. X-linked disorders include Wiskott-Aldrich
syndrome and a dyshematopoietic syndrome
resulting from a mutation in GATA-1, an important
transcriptional regulator of hematopoiesis
38. characterized by thrombocytopenia, a
microangiopathic hemolytic anemia evident by
fragmented RBCs and laboratory evidence of
hemolysis, and microvascular thrombosis.
thrombotic thrombocytopenic purpura (TTP) and
hemolytic uremic syndrome (HUS), as well as
syndromes complicating bone marrow
transplantation, certain medications and infections,
pregnancy and vasculitis.
39. In DIC, while thrombocytopenia and
microangiopathy are seen, a coagulopathy
predominates, with consumption of clotting factors
and fibrinogen resulting in an elevated prothrombin
time (PT), and often activated partial thromboplastin
time (aPTT).
The PT and aPTT are characteristically normal in
TTP or HUS.
42. Medication-related microangiopathic hemolytic
anemia may be
secondary to antibody formation (ticlopidine and
possibly clopidogrel) or
direct endothelial toxicity (cyclosporine, mitomycin
C, tacrolimus, quinine
Rx: application of plasma exchange.
43. Treatment: Thrombotic Thrombocytopenic
Purpura
Plasma exchange remains the mainstay of treatment
Glucocorticoids
other immunomodulatory therapies have been
reported to be successful in refractory or relapsing
TTP, including rituximab, vincristine,
cyclophosphamide, and splenectomy.
45. Treatment: Hemolytic Uremic Syndrome
Treatment of HUS is primarily supportive. In
D+HUS, many (~40%) children require at least some
period of support with dialysis
Plasma infusion or plasma exchange
46. Which of the following is false regarding thrombotic
thrombocytopenic microangiopathies ? Harrison’s
18th Ed. 969
A. Thrombocytopenia
B. Laboratory evidence of hemolysis
C. Abnormal PT and aPTT
D. Microvascular thrombosis
47. TTP is due to deficiency in the activity of ?
Harrison’s 18th Ed. 969
A. ADAMTS 11
B. ADAMTS 12
C. ADAMTS 13
D. ADAMTS 14
48. Features of Hemolytic Uremic Syndrome include all
except ? Harrison’s 18th Ed. 970
A. Chronic renal failure
B. Microangiopathic hemolytic anemia
C. Thrombocytopenia
D. Frequently preceded by an episode of diarrhea
49. Which of the following is not used in the treatment
of TTP ?
A. Platelet concentrates
B. Plasma exchange
C. Fresh-frozen plasma (FFP)
D. Solvent/detergent-treated plasma (SD-FFP)
50. answer
Plasma exchange remains the mainstay of treatment of
TTP.
Use of platelet concentrates and Desmopressin, or
DDAVP in the treatment of TTP is contraindicated as
it leads to extensive platelet aggregation in the CNS.
51. Thromobcytosis
Due to
(1) iron deficiency;
(2) inflammation, cancer, or infection (reactive
thrombocytosis); or
(3) an underlying myeloproliferative process
[essential thrombocythemia or polycythemia vera)
or, rarely, the 5q- myelodysplastic process.
52. Thrombocytosis is due to deficiency of ? Harrison’s
18th Ed. 970
A. Vitamin B12
B. Folic acid
C. Iron
D. Calcium
53. Qualitative Disorders of Platelet Function
autosomal recessive disorders Glanzmann's
thrombasthenia (absence of the platelet GpIIbIIIa
receptor) and Bernard Soulier syndrome (absence of
the platelet GpIb-IX-V receptor).
Both are inherited in an autosomal recessive fashion
and present with bleeding symptoms in childhood.
54.
55. Platelet storage pool disorder (SPD) is the classic
autosomal dominant qualitative platelet disorder.
This results from abnormalities of platelet granule
formation. It is also seen as a part of inherited
disorders of granule formation, such as Hermansky-
Pudlak syndrome
56. In which of the following disorders, there is absence
of the platelet GpIIbIIIa receptor ?
Harrison’s 18th Ed. 970
A. Glanzmann’s thrombasthenia
B. Bernard Soulier syndrome
C. Hermansky-Pudlak syndrome
D. Heyde’s syndrome
58. three major types and four subtypes of type 2
Not all patients with low VWF levels have bleeding
symptoms. Whether patients bleed or not will
depend on the overall hemostatic balance they
have inherited, along with environmental
influences and the type of hemostatic challenges
they experience.
Although the inheritance of VWD is autosomal,
many factors modulate both VWF levels and
bleeding symptoms. These have not all been
defined, but include blood type, thyroid hormone
status, race, stress, exercise, and hormonal (both
endogenous and exogenous) influences.
59. Patients with type O blood have VWF protein levels
of approximately one-half that of patients with AB
blood type; and, in fact, the normal range for
patients with type O blood overlaps that which has
been considered diagnostic for VWD. A mildly
decreased VWF level should perhaps be viewed more
as a risk factor for bleeding than as an actual disease
60. Patients with Type 2 VWD have functional defects;
thus, the VWF antigen measurement is
significantly higher than the test of function.
For types 2A, 2B and 2M, VWF activity is
decreased, measured as ristocetin cofactor or
collagen-binding activity.
In type 2A VWD, the impaired function is due
either to increased susceptibility to cleavage by
ADAMTS13, resulting in loss of intermediate and
high-molecular-weight multimers, or to decreased
secretion of these multimers by the cell.
61. Type 2B VWD results from gain of function
mutations that result in increased spontaneous
binding of VWF to platelets in circulation, with
subsequent clearance of this complex by the
reticuloendothelial system.
Type 2M occurs as a consequence of a group of
mutations that cause dysfunction of the molecule but
do not affect multimer structure.
62. Type 2N VWD is due to mutations in VWF that
preclude binding of FVIII. As FVIII is stabilized by
binding to VWF, the FVIII in patients with type 2N
VWD has a very short half-life, and the FVIII level is
markedly decreased. This is sometimes termed
autosomal hemophilia.
Type 3 VWD, or severe VWD, describes patients with
virtually no VWF protein and FVIII levels <10%.
63. Treatment: von Willebrand Disease
For type 1 VWD is 1-deamino-8-d-arginine
vasopressin (DDAVP, or desmopressin), which
results in release of VWF and FVIII from endothelial
stores.
DDAVP can be given intravenously or by a high
concentration intranasal spray (1.5 mg/mL).
The peak activity when given intravenously is
approximately 30 minutes, while it is 2 h when given
intranasally. The usual dose is 0.3 g/kg
intravenously or 2 squirts (1 in each nostril) for
patients >50 kg (1 squirt for those <50 kg).
64. Some patients with types 2A and 2M VWD respond
to DDAVP such that it can be used for minor
procedures.
For the other subtypes, for type 3 disease, and for
major procedures requiring longer periods of normal
hemostasis, VWF replacement can be given. Virally
inactivated VWF-containing factor concentrates are
thought to be safer than cryoprecipitate as the
replacement product.
65. Antifibrinolytic therapy using either -aminocaproic
acid or tranexamic acid is an important therapy,
either alone or in an adjunctive capacity, particularly
for the prevention or treatment of mucosal bleeding.
These agents are particularly useful in prophylaxis
for dental procedures, with DDAVP for dental
extractions and tonsillectomy, menorrhagia, and
prostate procedures.
It is contraindicated in the setting of upper urinary
tract bleeding, due to the risk of ureteral obstruction
66. Which of the following vWD type is most severe ?
Harrison’s 16th Ed. 676
A. Type I
B. Type IIA
C. Type IIB
D. Type III
