Simple way to explain primary haemostatic anomalies Easy to teach Platelet function as well as disorders of granules and their release reaction. A reader will find a few better resources. Outline is from introduction to explanation of every single anomaly. Happy reading

1. Platelet Disorders
DR. OKURUT EMMANUEL

2. Introduction
• Platelets are cell fragments that function in the clotting system.
• Thrombopoietin helps control the number of circulating platelets by
stimulating the bone marrow to produce megakaryocytes, which in
turn shed platelets from their cytoplasm.
• Thrombopoietin is produced in the liver at a constant rate and its
circulating level is determined by the extent to which circulating
platelets are cleared, and possibly by bone marrow megakaryocytes.
• Platelets circulate for 7 to 10 days. About one third are always
transiently sequestered in the spleen.

3. • The platelet count is normally 140,000 to 440,000/µL
depending on specific laboratory ranges.
• However, the count can vary slightly according to menstrual
cycle phase, decrease during near-term pregnancy
(gestational thrombocytopenia), and increase in response to
inflammatory cytokines (secondary, or reactive,
thrombocytosis).
• Platelets are eventually destroyed by apoptosis, a process
independent of the spleen.
• The hemostatic system consists of platelets, coagulation
factors, and the endothelial cells lining the blood vessels

4. Definition
• Platelet disorders include;
a) An abnormal increase in platelets (thrombocythemia and reactive
thrombocytosis).
b) A decrease in platelets (thrombocytopenia)
c) Platelet dysfunction (von Willebrand disease, Glanzmann
thrombasthenia)
d) Disorders of Secretion and Thromboxane Synthesis
• Any of these conditions, even those in which platelets are increased, may
cause defective formation of hemostatic plugs and bleeding.
• The risk of bleeding is inversely proportional to the platelet count and
platelet function. When platelet function is reduced (eg, as a result of
uremia or aspirin use), the risk of bleeding increases.

5. Epidemiology of Platelet Disorders
• Inherited hemostatic disorders are relatively rare. The prevalence of von
Willebrand disease has been estimated at 1 case per 1000-5000
population.
• In contrast, acquired hemostatic disorders are common, and ITP is one of
the most common autoimmune disorders. The acute self-limiting form of
ITP, which is observed almost exclusively in children, occurs at a rate of 5
cases per 100,000 population, and the chronic form, which is observed
mostly in adults occurs at a rate of 3-5 cases per 100,000 population.
• Unlike hemophilia, most inherited disorders of platelets are not X-linked,
and they are equally distributed in both sexes. Acute ITP is also observed
equally in both sexes. Chronic autoimmune thrombocytopenia is more
common in females than in males.

6. Classification of platelet disorders
• Platelets have a variety of disorders ranging from congenital and
acquired, to disorders of function, secretion and relation to other
hemostatic factors.
• Based on the different types and anomaly related to platelet,
anomalies are as described below;

7. Autoimmune Thrombocytopenias
• Immune thrombocytopenia(ITP)
• Gestational thrombocytopenia
• Hypertensive disorders in pregnancy
• Post transfusion purpura
• Neonatal alloimmune thrombocytopenia
• Drug Induced thrombocytopenia
• Thrombotic Thrombocytopenic Purpura
• Haemolytic Uremic syndrome

8. Immune thrombocytopenia
• Commonest autoimmune disorders caused by autoantibodies to
platelets.
• The antigenic target in most patients appears to be the platelet GP
IIb/IIIa complex (for aggregation).
• Platelets with antibodies on their surface are trapped in the
spleen, where they are efficiently removed by splenic macrophages.
• The mechanism of origin of these antibodies is not known. These
antibodies may be directed toward viral antigens and then cross-
react with platelet antigens. They persist because of the failure of
immune surveillance mechanisms to repress these antibodies.

9. • These antibodies can also react with the developing megakaryocytes
in the bone marrow, leading to decreased production of platelets
(ineffective thrombopoiesis).
• ITP occurs commonly in otherwise healthy individuals and only rarely
as the initial manifestation of lupus and other autoimmune disorders.
• Greatly associated with HIV/AIDS, incidence higher in females than
males
• ITP occurs in two distinct clinical types:
1. An acute self-limiting form observed almost exclusively in children
(five cases per 100,000 persons).
2. A chronic form, observed mostly in adults (three to five cases per
100,000 persons) and rarely in children.

10. ACUTE ITP
• Self limiting form observed almost exclusively in children 3-5years
(five cases per 100,000 persons)
• Most patients have a history of an antecedent acute viral syndrome
• Onset is sudden. Bleeding is usually mild, unless the platelet count
drops below 20,000/µl
• With platelet counts from 20,000/µL to 50,000/µL, petechiae and
ecchymoses are observed following mild trauma
• With platelet counts less than 10,000/µL, generalized petechiae,
ecchymoses, and mucosal bleeding occur
• With platelet counts below 2000/µL, widespread ecchymoses,
hemorrhagic bullae, and retinal hemorrhage occur.

11. • The presence of lymphadenopathy or splenomegaly suggests other
secondary causes of thrombocytopenia rather than ITP
• The peripheral smear shows a decreased number of platelets. Often,
the smear shows giant platelets, which is a reflection of increased
thrombopoietin-induced stimulation of the bone marrow.
Peripheral smear shows giant
platelets reflecting the increased
megakaryocytic mass in the marrow
Bone marrow in immune thrombocytopenia.
Bone marrow examination reveals an increased
number of megakaryocytes.

12. Chronic ITP• Typically observed in adults aged 20-40
years.
• Insidious onset, and a history of an
antecedent infection need not be
present.
• More common in females than in
males. As in childhood ITP, the bleeding
manifestations depend on the platelet
count.
• The diagnosis of ITP is established by
the exclusion of other causes of
thrombocythemia. The peripheral blood
film should be examined to rule out
thrombotic thrombocytopenic purpura
(TTP) (fragments) or spurious
thrombocytopenia resulting from
clumping
Spurious thrombocytopenia. The smear shows
clumping of the platelets and satellitism involving
neutrophils and platelets.

13. Gestational thrombocytopenia
• A mild thrombocytopenia, occurring during the 3rd trimester in
an otherwise healthy pregnancy with spontaneous resolution
postpartum and does not result in neonatal thrombocytopenia
• Cause not well understood.
• Some researchers speculate the cause to be dependent on
dilution, decreased production of platelets, or an increased
turnover
• How this can be distinguished from a mild form of ITP is not clear.

14. Hypertensive disorders of pregnancy
• Eclampsia /Preeclampsia
syndrome are associated with
increased platelet
turnover(placental micro clots),
even when the platelet count is
normal. Controlling hypertension
and delivering the fetus lead to
restoration of the platelet count.
• Occasionally, thrombocytopenia
is associated with hemolysis and
elevated liver enzymes (ie,
hemolysis, elevated liver
enzymes, and low platelet
[HELLP] syndrome). This serious
disorder often mimics TTP.

15. Post-transfusion purpura
• Platelet GP IIb/IIIa is a major
antigen in platelets and is
polymorphic. Most individuals have
leucine at position 33 (PLA1/PLA1 or
human platelet alloantigen [HPA]–
1a). A small number of individuals,
approximately 1-3% of random
populations, have proline at
position 33 (PLA1-Negative in
homozygotes).
• When PLA1-negative patients
receive blood products from HPA-
1a–positive individuals, they
produce an antibody reactive
against HPA-1a.
• This alloantibody destroys the
transfused platelets and the
patient's own platelets, leading to
a severe form of thrombocytopenia
usually 10 days after that lasts for
several weeks and, sometimes,
several months.
• Risk of post-transfusion purpura
were significantly higher with
platelet-containing transfusions,
greater number of units transfused,
and underlying health conditions
including a history of cardiac
arrhythmias, coagulopathy,
leukemia, and transplantation

16. Neonatal alloimmune thrombocytopenia
• The prevalence of one case in 200
term pregnancies; clinically
apparent disease in one case in
1500 term pregnancies; most
common cause of severe neonatal
thrombocytopenia.
• Occurs when maternal antibodies
against fetal platelet antigens
inherited from the father but
absent in the mother cross the
placenta and induce severe
thrombocytopenia. Most cases are
due to platelet antigens HPA-1a
observed in mothers who are HPA-
1b.
• Pathophysiology of this disease is
similar to that of the hemolytic
disease of the newborn. Unlike
hemolytic disease, however,
thrombocytopenia occurs during
the first pregnancy in 50% of cases.
• Diagnosis is considered when
bleeding or severe
thrombocytopenia occurs in a baby
after an otherwise uncomplicated
pregnancy.
• The affected infant may have
intracranial hemorrhage, and the
disorder is associated with a
relatively high mortality rate.

17. Drug-induced thrombocytopenia
• Drugs can induce thrombocytopenia by 3 mechanisms:
1. Cytotoxic drugs can inhibit platelet production in the bone marrow,
as can thiazide diuretics, interferon, and alcohol
2. Drug-induced thrombocytopenia can result from the immunologic
destruction of platelets. Drugs can induce antibodies to platelets,
either acting as a hapten or as an innocent bystander.
3. In addition, drugs such as gold salts and interferon can induce an
ITP-like disorder.

18. Common drugs associated with
thrombocytopenia
 Amiodarone
 Captopril
 Sulfonamides
 Glyburide (glibenclamide)
 Carbamazepine
 Ibuprofen
 Cimetidine
 Tamoxifen
 Ranitidine
 Phenytoin
 Vancomycin
 Piperacillin

19. • Heparin causes a unique situation among drug-induced
thrombocytopenias in that the antibodies also activate platelets and
induce a hypercoagulable state, so called Heparin-induced
thrombocytopenia.
• The diagnosis is often empirical. A temporal relationship must be
present between the initiation of the drug and the development of
thrombocytopenia, with no other explanations for thrombocytopenia.
• Identifying the drug that is causing severe thrombocytopenia in an
acutely ill patient who is taking multiple drugs is often challenging.

20. Thrombotic thrombocytopenic purpura (TTP)
• TTP is a rare but serious disorder
with a pentad of manifestations, as
follows:
1.Thrombocytopenia (with purpura)
2.Red blood cell fragmentation
3.Kidney failure
4.Neurologic dysfunction
5.Fever
• TTP results from the abnormal
presence of unusually large
multimers of von Willebrand
protein; normally synthesized in
the endothelial cells, are
hyperactive towards platelets.
• These large multimers are
processed to normal-sized
multimers by a plasma enzyme
identified as ADAMTS13, a
metalloproteinase synthesized in
the liver.

21. • The sporadic forms of TTP are caused by an antibody or toxin inhibiting the
activity of ADAMTS13.
• The chronic, recurrent form of TTP may result from a congenital deficiency of
the enzyme.
• The ultralarge multimers induce the aggregation of platelets, causing platelet
consumption
• Occlusion of microvasculature by the platelets in the brain, kidney, and other
organs leads to myriad symptoms. A TTP-like syndrome has been associated
with lupus, pregnancy, HIV infection, and certain drugs (quinine, ticlopidine,
clopidogrel, cyclosporine, chemotherapeutic agents).
• The most common presentation is petechiae and neurologic symptoms. The
neurologic symptoms can range from headache and confusion to seizures
and coma. Fever is present in slightly more than 50% of the patients

22. Hemolytic-uremic syndrome
• Hemolytic-uremic syndrome (HUS) is a clinical syndrome
characterized by progressive renal failure that is associated
with microangiopathic, hemolytic anemia and
thrombocytopenia.
• HUS is a catastrophic illness that predominantly affects
children aged 4-12 months, sometimes affects older children,
and rarely affects adults. HUS follows upper respiratory and
gastro-intestinal tract infections.
• Initial symptoms typically include bloody diarrhea, vomiting,
fever, and weakness; Kidney problems and low platelets then
occur as the diarrhea is improving.

23. • Most cases occur after infectious diarrhea due to a specific type of
E.coli, other causes include S.pneumonae, Shigella, Salmonella, and
certain medications.
• E. coli can produce stx1 and/or stx2 Shiga toxins, the latter being
more dangerous and a combination of both toxins in certain ratios is
usually associated with HUS. These Shiga toxins bind GB3
receptors, globotriaosylceramide, which are present in glomerular
epithelium.

24. • This action includes a cascade of signaling events leading
to apoptosis and binding of leukocytes to endothelial cells.
• The Shiga-toxin-activated endothelial cells then
become thrombogenic (clot-producing) by inducing the
release of cytokines and chemokines that activate platelet .
• Additionally, the binding action of Shiga-toxin inactivates
a metalloproteinase called ADAMTS13.
• Once ADAMTS13 is disabled, multimers of von Willebrand
factor form and initiate platelet activation, causing
microthrombus formation.

25. Disorders of Platelet Function
i. Von Wilebrand disease
ii. Bernard-Soulier syndrome
iii. Glanzmann thrombasthenia

26. Von Willebrand disease (vWD)
• Most common inherited bleeding disorder; autosomal
dominant, with prevalence is estimated to be one case per 1000
population
• Defective platelet adhesion to subendothelial components
caused by a deficiency of the plasma protein von Willebrand
factor(vWf). This factor is a large, multimeric glycoprotein that
is synthesized, processed, and stored in the Weibel-Palade
bodies of the endothelial cells, and secreted constitutively and
following stimulation.
• vWf has a major role in primary hemostasis as mediator of the
initial shear-stress–induced interaction of the platelet to the
subendothelium via the GP Ib complex.

27. • In addition, von Willebrand protein acts as a carrier and stabilizer
of coagulation factor VIII by forming a complex in the circulation.
• In the absence of vWf, the factor VIII activity level is low because of
a deficiency in its carrier protein(vWf).
• von Willebrand disease is a relatively mild bleeding disorder, except
in the occasional patient who is homozygous for the defect and
who has severe bleeding often indistinguishable from classic
hemophilia.
• The bleeding manifestations are predominantly skin-related and
mucocutaneous (i.e., easy bruising, epistaxis, GI hemorrhage).
• Most bleeding episodes occur following trauma or surgery.
• In women, menorrhagia is common, often exacerbated by the
concurrent administration of nonsteroidal anti-inflammatory drugs.

28. Variants of von Willebrand disease
• Variants result from qualitative abnormalities in the von Willebrand
protein.
• A common variant (type IIA) of von Willebrand disease results from
functionally defective vWf that is unable to form multimers or be more
susceptible to cleavage by ADAMTS13. Factor VIII level may be normal.
• In the type IIB variant, the von Willebrand protein has heightened
interaction with platelets, even in the absence of stimulation. Platelets
internalize these multimers, leading to a deficiency of von Willebrand
protein in the plasma.
• The type IIN (Normandy variant) is caused by defect in vWf to bind
coagulation factor VIII, resulting in the shortened half-life of factor VIII in
the plasma. The ristocetin-induced platelet aggregation and vWf antigens
are normal.

29. • Type IIM von Willebrand disease is due to a defect in binding to
platelet glycoprotein Ib but no defect in multimerization. In this
variant, the ristocetin cofactor activity and ristocetin-induced platelet
aggregation are decreased but the vWf antigen and multimers are
present in normal levels.
• A disorder of platelet GP Ib, mimicking type IIB von Willebrand
disease, has also been described. In this condition, increased affinity
for von Willebrand protein in the resting stage leads to the deletion of
plasma von Willebrand protein. This disease is called pseudo von
Willebrand disease or platelet-type von Willebrand disease.
• Type III von Willebrand disease is a severe form that is characterized
by very low levels of vWf and clinical features similar to hemophilia A,
but with autosomal recessive inheritance. This condition results from
a homozygous state or double heterozygosity.

30. Bernard-Soulier syndrome
• Results from a deficiency of platelet glycoprotein protein Ib, which
mediates the initial interaction of platelets with the subendothelial
components via the von Willebrand protein.
• It is a rare but severe bleeding disorder. Platelets do not aggregate to
ristocetin. The platelet count is low, but, characteristically, the platelets
are large, often the size of red blood cells, and may be missed on
complete blood counts because most automatic counters do not count
them as platelets.

31. Glanzmann thrombasthenia
• Results from a deficiency of the GP IIb/IIIa complex. Platelets do not
aggregate to any agents except ristocetin. The more severe type I
results from a complete absence of the GP IIb/IIIa complex, whereas
in the milder type II, some of the GP IIb/IIIa complex is retained.
• Both Bernard-Soulier syndrome and Glanzmann thrombasthenia are
characterized by lifelong bleeding. Although platelet transfusions are
effective, they should be used only for severe bleeding and
emergencies, because alloantibodies often develop in these patients

32. Disorders of Secretion and Thromboxane Synthesis
During primary hemostasis, thromboxane synthesis and
released ADP play a major role. A mild bleeding diathesis
ensues if these mechanisms are deficient.
• Thromboxane synthesis disorders are almost always caused
by aspirin and nonsteroidal anti-inflammatory drugs
(NSAIDs); Aspirin irreversibly inactivates cyclooxygenase in
platelets, its effect lasts throughout the life span of platelets,
which is approximately 1 week.
• Other NSAIDs are competitive inhibitors of cyclooxygenase,
and their effect on platelets depends on the half-life of the
drug. For example, the effect of ibuprofen, and most other
NSAIDs, lasts only 1 day.

33. • Mutations in the enzyme that converts arachidonic acid to
thromboxane A2 have been described and are associated with a
lifelong bleeding diathesis. Similarly, an absent or defective receptor
for thromboxane A2 also leads to an aspirin-like aggregation defect
• In disorders of release reaction, platelets fail to secrete
proaggregatory ADP following activation. The defects result from
either the absence of granules in platelets or the defective storage of
ADP. Inherited deficiency of ADP receptor P2Y12, characterized by
mild bleeding diathesis, has also been described.
• Platelet transfusions should be avoided as much as possible because
they can induce alloantibodies.

34. Platelet Dysfunction in Uremia
• Bleeding time is generally very prolonged. The bleeding has the
characteristics of a platelet disorder, and GI tract bleeding is the most
frequent manifestation.
• Platelet function in uremic patients improves after dialysis. A number
of dialyzable factors have been shown to inhibit platelet function.
Furthermore, uremic platelets synthesize less thromboxane A2, and
the blood vessels in patients with uremia produce greater quantities
of platelet-inhibitory prostaglandin.
• Nitric oxide produced by the endothelial cells inhibits platelet
function

35. Etiology of Platelet Disorders
• Platelet disorders include
a) An abnormal increase in platelets (thrombocythemia and reactive
thrombocytosis),
b) A decrease in platelets (thrombocytopenia),
c) Platelet dysfunction, and
d) Disorders of Secretion and Thromboxane Synthesis
• Etiology is described basing on the disorder

36. Thrombocythemia and thrombocytosis
• Essential thrombocythemia is a myeloproliferative neoplasm
(previously myeloproliferative disorder) involving overproduction of
platelets because of a clonal abnormality of a hematopoietic stem
cell. There is no correlation between the platelet count and risk of
thrombosis, but some patients with extreme thrombocytosis
(i.e.,>1,000,000/µL) develop bleeding due to loss of high molecular
weight von Willebrand factor multimers.
• Reactive thrombocytosis is platelet overproduction in response to
another disorder. There are many causes, including acute infection,
chronic inflammatory disorders (e.g., T.B, IBD, Rheumatoid arthritis,
sarcoidosis), Fe Deficiency, and certain cancers. Reactive
thrombocytosis is not typically associated with an increased risk of
thrombosis or bleeding.

37. Thrombocytopenia
• Causes of thrombocytopenia can be classified mainly by mechanism i.e.
1. Decreased platelet production
2. Increased splenic sequestration of platelets with normal platelet survival
3. Increased platelet destruction or consumption (both immunologic and
nonimmunologic causes)
4. Dilution of platelets
Genetic defects have been defined for 30 forms of inherited
thrombocytopenia, but the underlying genetic or molecular mechanisms
remain unidentified for nearly 50% of cases.

38. 1. Decreased platelet production
• Diminished or absent
megakaryocytes in bone
marrow
• [Aplastic anemia, Leukemia,
Myelosuppressive drugs (e.g.,
hydroxyurea, interferon alfa-2b,
chemotherapy drugs),
Paroxysmal nocturnal
hemoglobinura (some patients)].
• Diminished platelet production
despite the presence of
megakaryocytes in bone
marrow
• [Alcohol-induced
thrombocytopenia, Bortezomib
use, HIV-associated
thrombocytopenia,
Myelodysplastic syndrome
(some), Vit B12 deficiency or
folate deficiency].

39. 2. Increased splenic sequestration of platelets
with normal platelet survival
• Cirrhosis with congestive
splenomegaly
• Gaucher disease
• Myelofibrosis with myeloid
metaplasia
• Sarcoidosis

40. 3. Increased platelet destruction or consumption
• Immunologic destruction
• Antiphospholipid antibody syndrome
• Connective tissue disorders
• Drug-induced thrombocytopenia
• HIV-associated thrombocytopenia
• Immune thrombocytopenia
(autoimmune, alloimmune, drug-
induced)
• Lymphoproliferative disorders
• Neonatal alloimmune
thrombocytopenia
• Post-transfusion purpura
• Sarcoidosis
• Non-immunologic destruction
• Certain systemic infections (e.g.,
hepatitis, infectious mononucleosis,
cytomegalovirus infection, or dengue)
• Disseminated intravascular
coagulation
• Pregnancy (gestational
thrombocytopenia)
• Sepsis
• Thrombocytopenia in acute
respiratory distress syndrome
• Thrombotic thrombocytopenic
purpura-hemolytic-uremic syndrome

41. 4. Dilution of platelets
• Fluid replacement, massive RBC replacement or exchange transfusion
(most RBC transfusions use stored RBCs that do not contain many
viable platelets).
• Spurious thrombocytopenia can occur due to aggregates forming in
the specimen.

42. Disorders of platelet function
Inherited disorders of platelet
function are as follows:
• Disorders of platelet adhesion
(von Willebrand disease,
Bernard-Soulier syndrome)
• Disorders of aggregation
(Glanzmann thrombasthenia)
• Disorders of secretion
• Disorders of thromboxane
synthesis
• Acquired disorders of platelet
function may result from the
following:
• Drugs (e.g., aspirin, NSAIDs,
alcohol)
• Uremia
• Paraproteins
• Fibrin degradation products
• Myelodysplasia or a
myeloproliferative syndrome

43. Pathogenesis
• Platelet disorders lead to defects in primary hemostasis and produce signs
and symptoms different from coagulation factor deficiencies (disorders of
secondary hemostasis). The body's reaction to vessel wall injury is rapid
adhesion of platelets to the subendothelium. The initial hemostatic plug,
composed primarily of platelets, is stabilized further by a fibrin mesh
generated in secondary hemostasis. The arrest of bleeding in a superficial
wound, such as the bleeding time wound, almost exclusively results from
the primary hemostatic plug.
• Hence, primary hemostatic disorders are characterized by prolonged
bleeding time, and the characteristic physical examination findings are
petechiae and purpura. In comparison, defects in secondary hemostasis
result in delayed deep bleeding (eg, into muscles and joints) and the
characteristic physical examination finding is hemarthrosis. Hemarthrosis
and muscle hematomas are not present in primary hemostatic disorders.

44. Clinical Presentation of Platelet Disorders
Patient history
• History and physical examination findings help clinicians to distinguish
between primary and secondary hemostatic disorders and to
determine whether the disorder is inherited or acquired.
• Epistaxis, bleeding gums, bleeding from a tooth extraction,
hemoptysis, hematemesis, hematuria, hematochezia, melena stools,
Menstrual history of metromenorrhagia, PPH, excessive bleeding
following circumcision and other surgical procedures. History of blood
transfusions, drugs used, and iron therapy for anemia.

45. Physical examination
• Bruising is common
• Petechiae (pinpoint hemorrhages (< 2
mm) in the skin)
• Purpura, non-palpable (0.2-1 cm)
• Ecchymoses are larger hemorrhages.
• Initially, purpura tends to form in the
areas of increased venous pressure, such
as the legs. Petechiae and purpura may
develop following the application of a
sphygmomanometer cuff.
• Splenomegaly is not observed in the
typical patient with ITP. The spleen can
engulf platelets and be several times
normal size without becoming palpably
enlarged.
• Hemarthrosis and deep muscle
hematomas are unusual in patients with
primary hemostatic disorders.

46. Laboratory Studies
• A complete blood count and peripheral blood smear (ITP, TTP).
• In pediatric patients, immunoglobulin assays are often performed to
exclude common variable immune deficiency (CVID) as a cause of ITP.
• Structured bleeding assessment tools (BATs) such as from the International
Society on Thrombosis and Haemostasis (ISTH‐BAT) records both the
presence and the severity of bleeding symptoms covering 14 important
sites of bleeding in patients.
• Platelet-associated immunoglobulin G (less useful- non-specific)
• Test of primary hemostasis bleeding time (forearm, 1 mm, 1cm)
• In vitro platelet function analyzer 100 (assesses primary hemostasis under
shear stress).
• Platelet aggregation (turbidimetric methods); useful in distinguishing
different disorders of platelet function, and von Willebrand disease.
• Bone marrow aspiration and cytology

47. Imaging Studies
• Imaging studies are not necessary to diagnose uncomplicated ITPs.
Rarely, platelet survival studies may be necessary to document
decreased platelet survival before splenectomy in a patient with
possible bone marrow hypofunction. Typically, the platelet half-life is
decreased from the normal 5-7 days. A normal platelet survival curve
is not consistent with increased splenic destruction.
• In a patient who has relapsed following splenectomy, an indium-
labeled platelet imaging study is sometimes useful for localizing an
accessory spleen.
• In case of malignancies

48. Effect in OBGYN and Surgery
• Hemostasis must always be achieved following any surgical procedure
• Disorders of platelets make primary hemostasis compromised thus
requiring a lot of considerations both pre- and post-operatively.
• During labour, bleeding is expected from the “show” to the 4th stage,
including in puerperium. Platelet anomalies will mean excessive
bleeding (Gestational thrombocytopenia).
• Delayed hemostasis also implies increased wound sepsis rates thus
more costly, more life threatening, and more strenuous.
• Neonatal alloimmune thrombocytopenia is highly fatal in neonates.
• Wound healing is delayed as well in patients thus expensive in terms
of increased hospital stay, costs, infections, among others.

49. Management – general principles
• Careful assessment of the symptoms and appropriate laboratory
evaluation is important in making the decisions especially operatively.
• Family history, including consanguinity, are important.
• Many of these patients will be exposed to blood products in their life
span thus it is important that they are immunized against hepatitis A
and B, pneumococcal vaccines should be given, and annual liver
function tests should be part of their general surveillance.
• Platelet transfusion—use depending on the cause and severity of
thrombocytopenia and for emergencies.
• Discontinue NSAIDs, other antiplatelet agents, and anticoagulants.
• Treat the underlying cause.

50. Management options
Medical drug options
• Intravenous immune globulin (IVIG)
• Corticosteroids
• Anti-D immunoglobulin
• Thrombopoietin receptor agonist
(eltrombopag, Avatrombopag or romiplostim)
• Anti-platelet agents like Rituximab
• cytotoxic agents like Azathioprine or
Cyclophosphamide
• Monoclonal antibodies like eculizumab.
• Vasopressin analogues e.g. Desmopressin
(DDAVP)
• Anti‐fibrinolytics e.g. aminocaproic acid and
tranexamic acid.
Non-drug options
• Splenectomy
• Bone marrow
transplant
• Maternal platelets
radiation in alloimmune
neonatal
thrombocytopenia
• Plasma Exchange (TTP)
• Platelet transfusion
• Dialysis
• Gene therapy

51. Thrombocytopenic Purpura
1. Adrenal corticosteroids
2. IV immune globulin—saturates the reticulo-endothelial system
binding sites for platelet-bound self-immunoglobulin
3. Splenectomy—induces remission in 70% to 80% of the cases of
chronic ITP
4. Platelet transfusions—for life-threatening and serious hemorrhagic
episodes
5. Romiplostim and eltrombopag, have been approved for Splenectomy
resistant patients

52. Thrombotic Thrombocytopenic Purpura
1. Plasmaphoresis (large volume).
a. Begin as soon as diagnosis is established (delay in treatment is life-
threatening).
b. Response is usually good (monitor platelet count, which should
increase).
2. Corticosteroids and Splenectomy—may be of benefit in some cases.
3. PLATELET TRANSFUSIONS ARE CONTRAINDICATED

53. Heparin-induced Thrombocytopenia
1.stop heparin. If anticoagulation is indicated (venous thrombosis), give
a thrombin inhibitor such as lepirudin, argatroban, and dabigatran.
2. Avoid heparin in the future in any patient who has developed an
episode of HIT.

54. von Willebrand Disease
1. DDAVP (desmopressin)—induces endothelial cells to secrete vWF.
a. Treatment of choice for type 1 vWD (the most common type).
b. Some patients with type 2 vWD may respond to DDAVP, but it is not
effective in type 3 vWD.
2. Factor VIII concentrates (containing high-molecular-weight vWF).
a. Give to all patients with vWD (any type) after major trauma or during
surgery.
b. Recommended for type 3 vWD (and type 2 patients not responsive to
DDAVP).
3. Cryoprecipitate is not recommended as treatment for vWD because it
carries the
risk of viral transmission.
4. Avoid aspirin/NSAIDs as well as intramuscular injections (exacerbate
bleeding tendency)

55. Bone marrow transplant/Hematopoietic stem
cell transplantation
• Transplantation of multipotent hematopoietic stem cells, usually
derived from bone marrow, peripheral blood, or umbilical cord
blood; may be autologous (the patient's own stem cells are used),
allogeneic (the stem cells come from a donor) or syngeneic (from an
identical twin).
• Recipient’s immune system first detroyed by radiation
• Infection and graft-versus-host disease are major complications
• Bone marrow transplantation from HLA‐identical donors has shown
to be successful in BSS with severe hemorhagic symptoms