 Petechiae

 Purpura
 Ecchymoses

Mucosal Bleeding
 Epistaxis
 Gingival Bleeding
 GI bleeding
 Menorrhagia
 Hematuria
 Platelet count
 PBS
 IBT or PFA
 vWF studies (VIII:C, vWF antigen, vWF activity)
 Platelet antibody testing
 Flowcytometry (GP analysis, platelet associated IgG)
 Platelet aggregation studies (Lumiaggregometry, 51Cr release)
 BMA and biopsy
 characterized by a decrease in the number of circulating platelets.
The causes are:
 A. Pseudo-Thrombocytopenia
 B. Defective production of platelets in the bone marrow which may be
due to:
◦ 1. Decreased number of megakaryocyte which may be due to:
 Fanconi’s anemia
 Acquired disorders
 Marrow replacement by malignant cells
◦ 2. Ineffective platelet production which is seen in:
 Hereditary thrombocytopenia
 Megaloblastic Anemia
 di Guglielmo’s syndrome
 PNH
 C. Increased Destruction of platelets
◦ 1. Combined consumption of both platelet and coagulation as seen in:
 Toxicity due to snake venom
 Obstetric complications
 Neoplasm
 Bacterial and viral infections
 Intravascular hemolysis
◦ 2. Isolated consumption of platelets due to:
 Thrombotic thrombocytopenic purpura
 Hemolytic Uremic Syndrome
 Vasculitis
 Disseminated intravascular coagulation
3. Immune Destruction of Platelets
 Idiopathic Thrombocytopenic purpura
 Post-transfusion purpura
 Isoimmune neonatal purpura
 Drug induced antibody
D. Abnormal Platelet Distribution or Pooling
1. Hyperspleenism (Spenomegaly)
2. Hemangiomas (Kasabach-Merritt Syndrome)
E. Thrombocytopenia associated with HIV, severe
but rarely hemorrhagic. Characteristics are:
1. Abundant megakaryocytes
2. Occasional giant platelets
3. Immune origin
4. Absence of splenomegaly
 Also known as spurious thrombocytopenia.
 A relatively uncommon phenomenon caused by ex vivo
agglutination of platelets.
 Can be induced by antiplatelet antibodies or by
activation of the platelets during collection.
 Presence of these antibodies are responsible for clearing
aged and damaged platelets
 EDTA, sodium citrate, sodium oxalate, ACD and heparin
can cause platelet clumping
 Usually IgG type; some are IgM and IgA (directed against
GPIIb-IIIa)
 Antibodies directed against GPIIb-IIIa react with the
leukocyte Fc gamma receptor III and attach the platelets
to neutrophils and monocytes, inducing the
phenomenon.
 Platelets form a rosette around the periphery of
leukocytes.
 Neutrophils are the most frequently involved;
occasionally monocytes
 Naturally occurring, but exposure of antigen on EDTA-
treated platelets and leukocytes may trigger the
phenomenon.
 Antiplatelet antibodies from patients with
pseudothrombocytopenia cross-react with negatively charged
phospholipids and may exhibit cardiolipin activity.
 Lost their ability to clump platelets when adsorbed onto either
cardiolipin or activated normal platelets
 Antigen are negatively charged phospholipids on the surface
of platelets.
• Described in patients suffering from acute coronary
syndromes treated with the GpIIb-IIIa antagonist abciximab
• Abciximab has been associated both pseudo and true
thrombocytopenia
• Agglutinins bind GpIIb-IIIa at new epitopes induced by the
combination of abciximab binding and calcium chelation.
• Pseudothrombocytopenia (abciximab) is a benign laboratory
condition.
 Automated platelet
 Platelet clumping can be prevented
 Alternative use of sodium
 An accurate platelet count
ammonium oxalate
manual count using Burker chamber
 Autosomal Recessive Thrombocytopenia
 Autosomal Dominant Thrombocytopenia
 X-Linked Thrombocytopenia
Congenital Amegakaryocytic Thrombocytopenia (CAMT)
 Presence of severe thrombocytopenia, absence of
megakaryocytes in the bone marrow
 Family history is negative, both parents having normal platelet
counts and function
 Markedly elevated serum thrombopoietin
 Patients develop progressive marrow aplasia
 Group CAMT I
 Group CAMT II
Thrombocytopenia with Absent Radius (TAR)
 Rare disease, first identified in 1959
 Thrombocytopenia is moderate, approximately 50 X 103/uL
 Serum TPO levels are normal, and marrow cellularity is normal or
increased.
 Megakaryocytes are low in number, absent or appear immature
 Can be managed by platelet transfusion
 Mild thrombocytopenia characterized by a normal platelet
survival and normal number of bone megakaryocytes
 Thrombocytopenia (counts 20,000 to 100000/uL) or a history
of increased bruisability is apparent on early life.
 PBS shows platelet macrocytosis
 Abnormal platelet aggregation, normal platelet membrane
glycoproteins.
MYH9- related Thrombocytopenia Syndromes
 Caused by mutations in the MYH9 gene
 These include:
May-Hegglin anomaly
Sebastian syndrome and its variant
Epstein syndrome
Fechtner syndrome.
 Mild to moderate thrombocytopenia
 PBS revealed enlarged platelets with frequent giant
platelets
 Syndrome Macrothrom Dohle-like Nephritis Deafness Cataracts
bocytopenia bodies

May- Yes Yes No No No

Hegglin

Sebastian Yes Yes No No No

Fechtner Yes Yes Yes Yes Yes

Epstein Yes No Yes Yes No

Platelet-type von Willebrand’s Disease
• Autosomal dominant disorder with hereditary
thrombocytopenia
• Characterized by abnormal binding of large vWF multimers
of platelets
• Mild thrombocytopenia, increased ristocetin-induced
platelet aggregation
• Resembles type 2b von Willebrand’s disease
Mediterranean Macrothrombocytopenia
 Relatively common and mild form of
macrothrombocytopenia
 Italy and the Balkan peninsula
 Gene mutation to the short arm of chromosome 17 (GPIa)
 Genotype and phenotype are equivalent to that of carrier of
Bernard-Soulier syndrome
Paris-Troussaeu Syndrome
 an inherited disorder characterized by several congenital
anomalies including dysmegakaryopoiesis
 Clinical features:
 mild to moderate psychomotor retardation
 Trigonocephaly
 facial dysmorphism
 cardiac defects
 thrombocytopenia
 PBS shows abnormal platelets with giant granules
Gray Platelet Syndrome
• Bleeding tendencies and
classical abnormal platelet
morphology
• Alpha Granules are absent or
greatly reduced
• Continued leakage of growth
factors and cytokines into the
marrow, causing myelofibrosis
Wiskott-Aldrich Syndrome
 Originally described in 1937, is now known as X-linked
hereditary disorder associated with combined
immunodeficiency thrombocytopenia, small platelets,
eczema and an increased risk to autoimmune disorders and
cancer
 Microthrombocytopenia is the most consistent feature of
WASP-associated disease.
 Primarily results from marrow failure
 Decreased proliferation and differentiation of
megakaryocyte progenitor similar to aplastic
anemia
 MDS are clonal myeloid disorders characterized by blood
cytopenias in combination with a hypercellular marrow that
often exhibit dysplastic changes in any of the three
hematopoietic lineages.
 Patients with MDS often display functional abnormalities in
platelets resulting to bleeding.
 Presence of micromegakayocytes or micromononuclear
megakaryocytes in the BM
 Maturation of megakaryocyte is arrested in MDS.
Immune (Primary)
a. ITP
b. Post Transfusion Purpura
c. Neonatal Isoimmune Purpura
d. Drug Induced Thrombocytopenia
e. Heparin Induced Thrombocytopenia
Immune (Secondary)
a. Lymphoproliferative Disorders
b. SLE/ Collagen Vascular Disorder
c. Viral Infection
Microangiopathic Thrombocytopenia
a. Thrombotic Thrombocytopenic Purpura
b. Hemolytic Uremic Syndrome
c. DIC
Pregnancy-Associated Thrombocytopenia
a. Gestational Thrombocytopenia
b. Preeclampsia-eclampsia and HELLP syndrome
 A.K.A immune thrombocytopenia
 One of the most common disorders causing severe isolated
thrombocytopenia
 Caused by an autoantibody to the patient’s platelet
 No specific test to confirm presence of ITP rather diagnosis
thru exclusion
 Can be present in children and adults
 Young children may present with an immune
thrombocytopenia that typically develops acute with a 1to 2
week duration, usually with bruising or petechiae.
 Present an initial platelet count of less than 20 X 109/L
 Self-limiting, spontaneous remissions with or without
therapy in majority of the patient
 IgG and corticosteriods are often used to decrease the
period of thrombocytopenia
 Commonly presents in the 20-50 year old groups, chronic
disease process with a greater predilection for women

 Occasionally, patients will have immune thrombocytopenia

after a viral illness or exposure to drugs

 Platelet counts are typically less than 30 X 109/L in patients

who present with bleeding manifestations
 BM is characterized by an increased or normal numbers of
megakaryocytes
 Platelet lifespan
Shortened
circulating platelets are morphologically large
 Bleeding time may not be as prolonged
 Measurement of antibodies (IgG) specific for platelet surface
GP IIb//IIIa and Ib/IX may provide greater specificity but still
are not diagnostic.
 Splenectomy and cortocosteroids are the conventional
therapies.
 Occurrence of sudden onset of thrombocytopenia in 1 week
after transfusion of blood or blood products containing
platelets
 Majority of the cases are results of alloantibody directed
against the platelet antigen P1A1 (HPA-1a)
 It is believed that PTP results from anamnestic immune
response from prior exposure to the antigen; primary
immunization occurs usually during pregnancy
 Complement Fixation, release of 51Cr, or
14C-Serotonin are some of the reliable test to

detect and measure anti-P1A1 antibodies.

• Direct and indirect ELISA test: ELISA, Western Blot followed by
ELISA or RIA, platelet suspension immunofluorescence and
immunoprecipitation of radiolabeled glycoprotein IIIa.

• Plasmapheresis without exchange and intravenous IgG

infusions have been effective as treatment to hemorrhagic
complication.
• It result to from immunization of the mother by fetal platelet
antigen and placental transfer of maternal antibody
• It is most often caused by maternal alloantibodies to the P1A1
antigen
• It is uncommon disorder, generally affecting the first-born
child
• Infants who develop this disorder appear normal at birth but
within a few hours develop scattered petechiae and purpuric
hemorrhages, with platelet counts below 30 X 109/L
 Quinine has been recognized as one of the most frequent
causes of drug-induced thrombocytopenia; where it acts as a
hapten
 Drug most frequently cited: quinine, quinidine, salicylates,
thiazides and sulfa drugs
 Appears more frequently in the elderly due to increased usage
of medication
 Purpura occurs approximately 7 days after initial use of the
drug but may occur within 3-5 days owing to anamnestic
response.
 Most common DIT; 2nd most significant adverse effect of
Heparin.
 Type I: HAT (non-immune-mediated)
 Type II: HIT (immune-mediated)
 Unexplained drop in Plt ct usually occurring 5-14 days of
heparin therapy.
 Dx: SRA or ELISA
 Hodgkin’s disease and Non-Hodgkin’s lymphoma, CLL has
been associated with decreased platelet survival
 SLE manifests immune-mediated thrombocytopenia and
thrombocytoenia secondary to bone marrow suppression.
 Transiently-impaired megakaryopoiesis without a reduction in
marrow cellularity
 Chronic viral infections such as HIV or hepatitis may lead to
marrow hypocellularity and to thrombocytopenia in affected
individuals
 Mononucleosis, mumps and rubeola may be complicated by
severe thrombocytopenia
 Malaria is frequently associated with thrombocytopenia as a
result of increased destruction and splenic sequestration.
 Appears to be correlated between CD4+ T cell depletion, viral
load in plasma and the occurrence of thrombocytopenia
 Viral infection of hematopoietic cells, altered marrow
microenvironment or dysfunction of the RES contribute to
ineffective thrombopoiesis in HIV-related thrombocytopenia.
 Development of marrow fibrosis and marrow involvement by
AIDS-related lymphoma may also lead to thrombocytopenia.
 Antiretroviraltherapy is often effective course of action
 Intravenous IgG and anti-D globulin are found to be effective
treatment
 Corticosteroids may be effective but have the potential to
increase the risk of infection in immunocompromised
individuals
 Splenectomy may also be effective
 First described as a pentad of signs and symptoms that
include: thrombocytopenia, microangiopathic hemolytic
anemia, fever, neurologic abnormalities and renal dysfunction
 Hyaline microthrombi are the characteristic pathologic feature
and are found in multiple organs
 Coagulation screening tests and D-Dimer assay are NORMAL
in TTP, in contrast to DIC which they are abnormal
 Two types of TTP: acquired and hereditary
 Thrombi found most extensively in the heart, pancreas,
spleen, kidney, adrenal gland and brain and are composed
mainly of platelets and vWF
 Associated with ADAMTS13 deficiency (a disintegrin-like and
matalloprotease with thrombospodin motifs) and is found in
most cases.
 ADAMST13 is also decreased in sepsis, DIC, and liver disease
 Thrombocytopenia and hemolysis, with the blood smear
showing polychromasia, basophilic stippling, nucleated cells,
schistocytes
 Platelet counts below 20 X 109/L at first presentation
 Reticulocyte count increased
 Bone marrow studies reveal erythroid hyperplasia, increased
number of megakaryocytes and occasionally microvascular
hyaline thrombi
 Screening tests are usually normal and FDP may be slightly
increased
 Serum lactic dehydrogenase (LDH) and unconjugated bilirubin
concentrations are invariably increased.
 Hemolysis is of the intravascular type: haptoglobin levels are
reduced and hemoglobinuria and hemosiderinuria usually are
present
 LDH levels and platelet counts are sensitive indices of the
response of the disorder to therapy;
 Proteinuria and microscopic hematuria are present in most
cases
 Blood urea nitrogen (BUN) and creatinine are normal or
slightly elevated
 Liver function tests are usually normal
 Analysis of the cerebrospinal fluid is rarely indicated but may
reveal an increased protein concentration and xanthochromia
 ADAMST13 binding IgG is detectable by enzyme-linked
immunoabsorbent assay (ELISA) in 97-100% TTP cases
 A.k.aSchulman-Upshaw syndrome or Chronic Relasping TTP
 Rare disorder believed to be < 1% of the TTP cases
 In the typical cases, the affected neonate is born with
meconium stain or presents within a few hours after birth with
neonatal distress, jaundice and thrombocytopenia
 Hemolysis with schistocytes on blood smears may be noted
 Hereditary TTP responds to 10-15 mL of FFP per kilogram of
body weight administered every 2 to 3 weeks.
 Syndrome of small vessel renal thrombi, microangiopathic
hemolysis that occurs following a prodrome of hemorrhagic
diarrhea
 Characterized clinically by microangiopathic hemolytic anemia
thrombocytopenia and renal failure
 More commonly seen in the pediatric population
 Pathologic thrombi are almost always limited to the
glomerular capillaries and afferent arterioles of the kidney
 Infection with Enterohemorrhagic Escherichia coli serotype
0157:H7
 Infection with Enterohemorrhagic Escherichia coli serotype
0104:H4 and Shigella dysenteriae serotype 1 have been
implicated as causative agents
 Appearance of dark-red or nearly black urine, that may
quickly lead to oliguria or even anuria
 External complications may occur and may include:
pancreatitis, glucose intolerance, colonic necrosis and
perforation, MI, pericardial or pleural effusion, acute
respiratory distress syndrome
 Hemoglobinemia is marked
 PT, PTT are usually normal to minimally prolonged, FDP or D-
Dimers are frequently elevated
 Serum haptoglobin levels are low or absent
 Bilirubin level is usually elevated; liver transaminases and
amylase may also be elevated
 BUN and creatinine levels are very high
 Urine usually contains hemoglobin and hemosiderin in
addition to albumin; RBC leukocytes and casts are also
present
 Characteristics TTP HUS

Age onset Adult Children

Organ involvement Multiple Kidney

Hematologic abnormalities
Microangiopathic HA Yes Yes
Thrombocytopenia Yes Yes

Neurological abnormalities Yes Rare

Renal complications Renal abnormalities Renal failure

 Caused by many illnesses, sepsis, obstetric emergencies and
severe trauma, and may cause bleeding
 Chronic form may be seen in cancer and may result in
thrombosis rather than bleeding
 Thrombocytopenia is usually seen in acute DIC
 Platelet count may be normal or elevated in chronic DIC
 DIC appears to be accelerated platelet destruction in
combination with coagulation factors consumption
 Preeclampsia- defined by hypertension and proteinuria;
usually becomes evident during second trimester and is a
major contributor to maternal and fetal morbidity and
mortality
 Eclampsia- defined by the occurrence of acute neurologic
abnormalities in a preeclamptic woman during peripartum
period
 Connection with thrombocytopenia, in a manner that blood
coagulation is activated and is detected by elevated FDP and
thrombin-antithrombin process
 Low level of ADAMTS13 is detected
 Disorder related to preeclampsia/eclampsia and is seen in the
peripartum period and defined by the presence of
microangiopathic HA, elevated liver enzymes, and low platelet
count
 HELLP (hemolysis, elevated liver enzymes, low platelet count)
• Mild thrombocytopenia with platelet counts of 50-80 X 109/L
• Commonly develops in the 3rd trimester of pregnancy and
does not cause bleeding in the mother or infant
• Low platelet count returns to normal after delivery
 Hypersplenism (splenomegaly)
 Hemangiomas (Kasabach-Merritt syndrome)
 May lead to thrombocytopenia by inducing a reversible
pooling up to 90% of total body platelets
 Platelet production is usually normal
 Chronic liver disease with portal hypertension and congestive
splenomegaly
 Most common disorder causing thrombocytopenia
 Itis distinguished from uncomplicated splenomegaly in that
pooling is accompanied by increased destruction of platelets,
leukocytes and erythrocytes in association with increased
marrow precursors of the deficient and correction of the
cytopenia by splenectomy
 Profound thrombocytopenia related to platelet trapping within
a vascular tumour, either a Kaposi-like
hemangioendothelioma or a tufted angioma
 Thrombocytopenia is usually severe and associated with DIC
 Contributing factors include “platelet trapping” and platelet
consumption associated with DIC.
 Platelet trapping demonstrated by immunohistochemical
staining of the tumours with anti-CD61 antibodies.
II. Thrombocytosis
- is characterized by an increase in the circulating platelet counts greater
than 450,000/uL.
A. Primary/ Essential Thrombocytosis
- The result of primary bone marrow disorder. It is characterized by an
increase number of platelets which is a result of clonal proliferation
that affects all hematopoietic cells. Patients have bleeding tendencies
because of platelet function abnormalities. It is most commonly seen in
patients with the following disorders:
1. Hodgkin’s disease
2. Polycythemia vera
3. Myelofibrosis
4. CML
5. Thrombocythemia
B. Reactive/ Secondary thrombocytosis
- a secondary response most associated with the following
disorders:
1. IDA associated with chronic blood loss
2. Chronic inflammatory disease may be associated with high
platelet counts.
3. Splenectomy-associated thrombocytosis
4. Rebound thrombocytosis, which may occur after a platelet
depletion through a massive blood loss.
- TPO levels in plasma are decreased
- Promoted by different types of drug like epinephrine, recombinant
IL11 (Oprevelkin)