PLATELET

DISORDERS
1. QUALITATIVE PLATELET
DISORDERS
2. QUANTITATIVE PLATELET
DISORDERS
a.THROMBOCYTOSIS
b.THROMBOCYTOPENIA

QUALITATIVE PLATELET DISORDERS

Qualitative platelet disorders are suggested by a prolonged bleeding
time or clinical evidence of bleeding in the setting of a normal
platelet count and coagulation studies.
Most commonly acquired, but can be inherited.

Tests are used to diagnose a platelet function disorder

Patient suspects a platelet function disorder :
1. Complete family history.
2.Laboratory tests :
Bleeding time This measures the length of time it takes for a simple
cut to stop
bleeding.
Platelet aggregation studies These measure if there are
abnormalities in the way
platelets clump together.
Von Willebrand Factor studies These find out if the Von Willebrand
Factor protein is
working normally and rule out this similar disorder as the cause of the
bleeding.

ACQUIRED PLATELET DYSFUNCTION

1.DRUG-INDUCED
The most common drug is
a. aspirin ( the need to hold aspirin for 5 days before elective surgery).
b.Other drugs clopidogrel, ticlopidine, and glycoprotein IIb/IIIa
inhibitors.
c.NSAIDs inhibit cyclooxygenase reversibly.
Ethanol use and aspirin therapy have synergistic effects.
Treatment : discontinuation of the culprit drug, and in clinically
significant bleeding is platelet transfusion .
2.UREMIA
It imparts a predisposition to bleeding that is incompletely
understood.
The treatment involves correction of anemia, institution of hemodialysis,
and the use of desmopressin /DDAVP
Platelet transfusions do not correct the coagulopathy because the
transfused platelets will assume the dysfunction of the uremic platelets.

3.LIVER DISEASE
Whether acute or chronic, is associated with platelet dysfunction that is
multifactorial in origin: increased FDPs from activation of the fibrinolytic
pathway compromise platelet function, and release of platelet factor 3
from platelets is impaired in patients with cirrhosis or other cause of hepatic
dysfunction.
4.ACQUIRED VON WILLEBRAND DISEASE
5.PARARANEOPLASTIC PLATELET DYSFUNCTION
It has also been associated with plasma cell dyscrasias and related to coating of
the platelet membrane with paraproteins.
Myelodysplastic and myeloproliferative syndromes may result in platelet
dysfunction .
The bleeding time is often prolonged but does not correlate with the bleeding
tendency.
Miscellaneous disorders associated with platelet dysfunction include:
cardiopulmonary bypass or valvular defects, autoimmune disorders (systemic
lupus erythematosus, rheumatoid arthritis, scleroderma), and severe iron or
folate deficiency.

INHERITED PLATELET DISORDERS

They include the common von Willebrand disease and the less common
Glanzman's thrombasthenia and Bernard-Soulier disease.
VON WILLEBRAND DISEASE

mild disease is often difficult to interpret.

Pathophysiology and Types:
VWD is subdivided into three types based on clinical and laboratory features (Table 4).44,45
,47

Type 1
It accounts for 70% of patients, has an autosomal dominant inheritance, and represents a
quantitative deficiency of vWF. Bleeding can be mild to moderately severe. 53,54
Type 2
It is further subdivided into the following:
Type 2A: accounts for about 15% of patients, is transmitted in an autosomal dominant
fashion, and involves a deficiency of the high-molecular-weight multimers of vWF. 53,54
Patients present with moderate to severe bleeding.
Type 2B: accounts for approximately 5% of patients, is inherited in an autosomal dominant
fashion, and involves a gain-of -function mutation that results from increased binding of
vWF to platelet glycoprotein 1B and resultant decreased circulating vWF. 53,54 The hallmark
of type 2B vWD is an enhanced aggregation of the patient's platelets in the presence of
Ristocetin. Patients with type 2B often have mild thrombocytopenia. Bleeding is moderate
to severe.
Type 2M: is rare, autosomal dominant, and characterized by reduced binding of vWF to
platelet glycoprotein 1B.53,54
Type 2N: This subtype is a rare, autosomal recessive disorder characterized by decreased
binding of vWF to factor VIII, resulting in low factor VIII levels and bleeding patterns similar
to that seen in the hemophilias.53,54
Type 3
It is rare, autosomal recessive subtype, characterized by a marked decrease in vWF. It
may result from different genetic defects in compound heterozygotes. 53,54
Treatment of vWD
Treatment of vWD is difficult to monitor because of the lack of laboratory tests that
correlate with bleeding. Hence, commonly monitored parameters include clinical bleeding,
factor VIII levels, and ristocetin cofactor. 46,48-5

DDAVP
DDAVP promotes the release of vWF from endothelial cells. It is effective for patients with type 1 disease,
has a varying effect for patients with type 2A disease, is relatively contraindicated in patients with type 2B
disease. DDAVP may also be helpful for patients with type 2M or 2N, but is not helpful for patients with type
3.43 DDAVP can be given intravenously or subcutaneously at 0.2 g/kg (maximum dose, 20 g) with a
response noted as early as 30 minutes later and lasting 6 to 12 hours. 43 The dose may be repeated in 12
hours and then daily. The intranasal preparation is given at a dose of 150 g for patients weighing less than
50 kg and 300 g for those weighing more than 50 kg. A trial infusion is needed to assess the efficacy of
treatment and adequacy of prophylactic use. Adverse effects include facial flushing, headaches,
hyponatremia with continuous use, and a potential for thrombotic events.43
For serious bleeding or prior to major surgery, intermediate-purity factor VIII concentrate is used to maintain
factor VIII levels between 50% and 100% for 3 to 10 days. A dose of 20 to 30 IU/kg is typically used twice
daily.48-51
-Aminocaproic acid (EACA) at a dose of 50 mg/kg four times daily) and tranexamic acid (25 mg/kg three
times daily) have been used for mild bleeding episodes and for dental procedures. They carry a risk of
thrombotic events.48-51
Topical treatment for oral/nasal bleeding with Gelfoam or Surgicel soaked with thrombin has been used
successfully.48-51
Recombinant factor VIIa has been used successfully in patients who have type 3 vWD with alloantibodies.

QUANTITATIVE PLATELET DISORDERS

THROMBOCYTOSIS
Thrombocytosis is the presence of high platelet counts in the
blood ( > 450.000/mm3)
Counts over 750,000 (and especially over a million) are
considered serious enough to warrant investigation and
intervention.
Definition
Thrombocytosis is a blood disorder in which the body produces a
surplus of platelets (thrombocytes).
Description
Thrombocytosis is an abnormally increased number of platelets in
the blood.
Throbocytosis is classified as one of two types.
Secondary thrombocytosis can be traced to another cause, such
as inflammation, severe bleeding, iron deficiency, or some
cancers.
Primary thrombocytosis (or essential thrombocythemia) is a single
disease entity, with unique clinical characteristics.

Causes and symptoms

The cause of essential thrombocytosis is unknown.
Secondary thrombocytosis may develop as a result of:
acute hemorrhage or infection
anemia
arthritis and other chronic inflammations
cancer
exercise
iron deficiency
medication
csteoporosis
removal of the spleen (splenectomy)
polycythemia vera (a disorder affecting other red blood cells, as well as
platelets)
stress
surgery
Symptoms
Two of every three patients who have thrombocytosis do not have any
symptoms of the disease at the time of diagnosis. Younger patients may
remain symptom-free for years.
Enlargement of the spleen is detected in 60% of patients with thrombocytosis.
The liver may also be enlarged. As many as half of all patients experience
bleeding from the skin, gums, or nose; and 20-50% have some blockage of
veins or arteries.
Other symptoms of thrombocytosis include:

Other symptoms of thrombocytosis include:

bloody stools
bruising
dizziness
headache
hemorrhage
prolonged bleeding after having surgery or after having a tooth pulled
redness or tingling of the hands and feet
weakness. In rare instances, the lymph nodes become enlarged
The highest platelet counts usually produce the most severe
symptoms. Younger patients (especially women) may not have
symptoms, even though their platelet counts are very high.
Complications
Complications of thrombocytosis include stroke, heart attack, and
formation of blood clots in the arms and legs.
Should be notified whenever bleeding is unexplained or
prolonged or the patient develops:
chest or leg pain
confusion
numbness
weakness

Diagnosis
The patient's symptoms suggest the presence of thrombocytosis.
Blood tests confirm the diagnosis.
Bone marrow aspiration (removal of a tissue sample for microscopic examination) may
also be performed.
Treatment
The key to treating secondary thrombocytosis is treating the underlying condition.
Any patient who has thrombocytosis should be encouraged not to smoke.
In young people who have no symptoms, this condition can remain stable for many years.
These patients should be monitored by a physician, but may not require treatment.
Treatment for patients who do have symptoms focuses on controlling bleeding,
preventing the formation of blood clots, and lowering platelet levels.
Treatment for secondary thrombocytosis involves treating the condition or disease
responsible for excess platelet production.
1.In 1997, the United States Food and Drug Administration (FDA) approved the use of
anagrelide HCl (Agrylin) to reduce elevated platelet counts and decrease the risk of clot
formation.
2.Some patients have benefited from the use of hydroxyurea, an anti-cancer drug.
3.Low doses of aspirin may prevent clotting, but can cause serious hemorrhages.
4.If drug therapy does not bring platelet counts down to an acceptable level as rapidly as
necessary, plateletpheresis may be performed.
This Procedure Consists Of:
withdrawing blood from the patient's body
removing platelets from the blood
returning the platelet-depleted blood to the patient

Prognosis
Many patients with thrombocytosis remain free of
complications for long periods. However, some
patients may die as a result of blood clots or
uncontrolled bleeding.
Prevention
There is no known way to prevent thrombocytosis.

THROMBOCYTOPENIA
Definition
Thrombocytopenia is defined as a platelet count less than
150,000/mm3
Thrombocytopenia is the medical term for a low blood platelet count.
It can be caused by
1. PLATELET UNDERPRODUCTION --- megakaryocytes
2. PLATELET SEQUESTRATION --- Hypersplenism
3. INCREASED PLATELET DESTRUCTION --- megakaryocytes

Common Signs and symptoms of a low blood platelet

count may include:
Petechiae
Superficial bleeding into the skin that appears as a rash of pinpointsized reddish-purple spots (petechiae), usually on the lower legs
Easy or excessive bruising
Prolonged bleeding from cuts
Spontaneous bleeding from gums or nose
Blood in urine or stools
Unusually heavy menstrual flows
Profuse bleeding during surgery
Complications may range from none to severe bleeding.
Thrombocytopenia usually improves by treating the underlying cause.
If bleeding is severe--- need a blood or even a platelet transfusion.

1.PLATELET UNDERPRODUCTION
The hallmark of platelet underproduction is decreased marrow
megakaryocytes (or, when available, a decreased peripheral
blood reticulated platelet count).
Common causes
1.infections (including HIV);
2.drugs (frequently chemotherapy or ethanol, but other
medications in rare instances);
3.radiotherapy; vitamin deficiency (folate or vitamin B 12);
4.marrow infiltration by tumor, storage disease, or marrow
failure syndromes (such as myelodysplastic syndrome, acute or
chronic leukemias).
Management
1.treatment of the underlying condition
2.supportive platelet transfusions if needed.
3.More recently, two recombinant thrombopoietin (TPO) made
their way into the clinical arena for the treatment of
chemotherapy-induced thrombocytopenia (recombinant human
thrombopoietin rHuTPO and pegylated recombinant
megakaryocyte growth and development factor PEG-rHuMGDF).

2.PLATELET SEQUESTRATION
Hypersplenism from a variety of causes including liver disease or
malignancy may result in platelet sequestration . Mild to moderate
thrombocytopenia is caused by platelet sequestration when there is an
associated mild reduction in neutrophil count and hemoglobin and with
minimal impairment of hematopoiesis on bone marrow examination.
If physical examination fails to detect splenomegaly evaluation with
ultrasonography or radionuclide imaging is recommended to
document splenomegaly.
Management
treatment of the underlying condition and platelet transfusion as needed.
Cytopenias secondary to hypersplenism are often not sufficiently severe
to warrant treatment in the form of (total or partial) splenectomy,
partial splenic embolization or transjugular intrahepatic portosystemic
shunting for congestive splenomegaly.

Causes of Splenomegaly
Cirrhosis
Heart failure
Portal or hepatic venous thrombosis
Malignancies and hematologic disorders, including lymphoma, acute and
chronic leukemias, myeloproliferative disorders, metastatic solid tumors,
and hemolytic anemias
Infectious disorders, including infection with Epstein-Barr virus,
cytomegalovirus, Salmonella, Brucella, tuberculosis, malaria,
Toxoplasma, and leishmania
Infiltrative disease, including Gaucher's disease, amyloidosis, and
glycogen storage diseases
Miscellaneous disorders, including sarcoidosis, systemic lupus
erythematosus, and Felty's syndrome

3.INCREASED PLATELET DESTRUCTION

The hallmark is increased marrow megakaryocytes
(or, when available, high reticulated platelet count).
Platelet destruction results from a variety of immune
conditions including the following:
Immune thrombocytopenic purpura
Thrombotic microangiopathies
Post-transfusion purpura (PTP)
Heparin-induced thrombocytopenia (HIT)
Disseminated intravascular coagulation (DIC).

IMMUNE THROMBOCYTOPENIC PURPURA (ITP)

The incidence of ITP 100 cases per 1 million person-years, with half the
cases occurring in the pediatric age group.
Adult onset is more likely to be chronic and insidious.
Adult onset ITP is more common in females than males (with a female to
male ratio of 1.7:1) while childhood onset has equal gender distribution.
ITP is subdivided into chronic or acute, with the latter being of 6 months or
less in duration.
Etiology:
ITP can be either primary or secondary.
Causes of secondary ITP include systemic lupus erythematosus,
antiphospholipid antibody syndrome, IgA deficiency, common variable
hypogammaglobulinemia, lymphoproliferative disorders (chronic lymphocytic
leukemia, lymphomas), viral (HIV, hepatitis C), or drug-induced (many drugs
have been linked to thrombocytopenia, but those known to be associated
with immune thrombocytopenia are heparin and quinidine).
Patients with drug induced ITP usually present within 1-2 weeks from
the initiation of the offending drug with petechiae, and a platelet
count less than 20,000/mm 3. Recovery usually occurs 5-7 days after
discontinuation of the offending agent but can occasionally be more
prolonged.
I
Pathophysiology:

PATHOPHYSIOLOGY:
The pathophysiology of primary ITP involves the formation of antiplatelet antibodies,
frequently directed at platelet glycoproteins IIb/IIIA, IIb/IX, Ia/IIa, V, or multiple platelet
antigens.
CLINICAL FEATURES:
On history and physical examination, the absence of systemic symptoms is helpful in
ruling out secondary causes. Evidence of platelet-type (mucosal) bleeding should be
noted, and the absence of splenomegaly supports the diagnosis. Bleeding is often less
pronounced than in cases of decreased production with similar platelet counts. 13-15,17
DIAGNOSIS:
1. CBC should be unremarkable except for thrombocytopenia or easy-to-account-for
anemia.
2.The peripheral smear must confirm thrombocytopenia, and large, immature
platelets
3.A bone marrow biopsy or aspirate is required only in patients older than 60
years; in the presence of atypical features (which include fatigue, fever, joint
pain, macrocytosis, and neutropenia); or before performing splenectomy in the patient
whose diagnosis is not secure.
4..Testing for antiplatelet antibodies is generally not recommended. Antiplatelet
antibodies have a sensitivity of 49% to 66%, a specificity of 78% to 92%, and a
positive predictive value of 80% to 83%. A negative test result does not rule out the
diagnosis.

TREATMENT:

First presentation
1.Steroids:
In the asymptomatic patients with a platelet count less than 30,000/mm 3 or in
the symptomatic patient with a platelet count greater than 30,000/mm 3 but
less than 50,000/mm3, treatment with Prednisone at a dose of 1 to 1.5
mg/kg/day has an expected response rate of 50%-75%. A response is usually
seen after days of treatment but the expert panel from the American society
of hematology differ on the length of time needed before changing therapy
from 1 week to 3 weeks.
2.Intravenous immunoglobulin (IVIG)
dose of 1 g/kg/day for 2 to 3 days is used to treat major bleeding, platelets
counts less than 5,000/mm 3 despite 3 days of steroids, or extensive and
progressive purpura. It is also the initial agents in patients with platelet counts
less than 50,000/mm3 with life threatening bleeding. The response rate for
IVIG is 80%. Disadvantages include cost, the low rate of long-term response,
and risks of anaphylaxis (especially in patients with IgA deficiency), renal
failure, or pulmonary failure.
3.Splenectomy
should be considered after 3 to 6 months if the patient continues to require 10
to 20 mg/day of prednisone to keep the platelet count greater than
30,000/mm3 or within 6 weeks of diagnosis in the patients with platelet counts
less than 10,000/mm3 despite treatment.

Urgent treatment for ITP patients with neurologic deficits or internal

bleeding, or for emergency surgery, includes methylprednisolone at a
dose of 30 mg/kg/day for 2 to 3 days for a maximum of 1 gram per day
and/or IVIG at a dose of 1 g/kg/day for 2 to 3 days, combined with
platelet transfusions. Vincristine, antifibrinolytic therapy, recombinant
factor VIIa, or continuous platelet transfusions should also be considered.

First relapse
Treatment is indicated only for platelet counts less than 30,000/mm 3.
Splenectomy (with a 66% response ratTre) is indicated in patients who
relapse and do not respond to treatment with steroids, IVIG, or anti-D
immune globulin.Anti-D immune globulin is traditionally less effective in
patients with ITP refractory to treatment.

When to seek medical advice

Have abnormal bleeding or bruising
Develop a rash of pinpoint-sized red spots (petechiae)
Because some of the underlying causes of
thrombocytopenia are serious, it's important to
promptly evaluate any signs or symptoms.
If the patient taking heparin and have severe or
increasing pain in leg---may be an indication of a
blood clot deep in a vein in leg.

Lifestyle and home remedies

If platelet count is low
- avoiding drugs such as aspirin, which may impair platelet function, and
avoiding
excessive alcohol intake.
- avoid contact sports, which can put you at a higher risk of injury and
bleeding.

THE

END