This document summarizes various platelet disorders including their causes, characteristics, diagnosis and treatment. It discusses decreased platelet production from bone marrow issues as well as increased platelet destruction from immune or non-immune causes. Specific disorders covered include idiopathic thrombocytopenic purpura, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, sequestration, Kasabach-Merritt syndrome, and others. Diagnostic tests and treatment approaches are provided for each condition.
2. Megakaryopoiesis
• Platelets are non-nucleated cellular fragments produced
by megakaryocytes within the bone marrow
• When the megakaryocyte approaches maturity, budding
of the cytoplasm occurs and large numbers of platelets
are liberated.
• Platelets circulate with a life span of 10-14 days.
• Thrombopoietin (TPO) is inversely related with platelet
number and megakaryocyte mass.
3.
4. Thrombocytopenia
• Reduction in platelet count to <1.5lakhs
• Causes
• Decreased production-congential /acquired
• Sequestration
• Increased destruction-immune/nonimmune
5.
6.
7. Idiopathic thrombocytopenic
purpura
• Most common cause
• 1 in 20,000
• Peak age is 1-4yr
• M=F
• Late winter and spring
• 1-4week after exposure to a common viral infection(50-65%)
an autoantibody directed against the platelet surface
• The antibody binds to the platelet surface , circulating
antibody-coated platelets are recognized by the Fc receptor on
splenic macrophages, ingested, and destroyed
• Viruses associated with ITP – EBV and HIV
8. • Clinical manifestations
• previously healthy 1-4 yr old child with sudden onset of
generalized petechiae and purpura
• Bleeding from gums and mucous membranes(<1lakh)
• Preceding viral infection
• Rare-splenomegaly,lymphadenopathy,bone pain,pallor
9. • Outcome
• Spontaneous resolution occurs within 6months(70-80%)
• <1% of patients develop ICH
• 20% with acute ITP progress to chronic ITP
• Outcome may be related to age
• Laboratory findings
• Severe thrombocytopenia
• Platelet size –normal/increased
• Hb,TC,DC-normal
• Bone marrow-normal/increased megakaryocytes.Some-
immature
10. • Indications of bone marrow aspiration/biopsy
• Abnormal TC/DC
• unexplained anemia with findings suggestive of a bone marrow
failure syndrome or malignancy
• Other tests
• HIV
• Platelet antibody testing
• DCT
11. • Treatment
• Antiplatelet antibodies bind to transfused platelets so it is
contraindicated
• Education and counseling
• Single dose of IVIG(0.8-1g/kg) for 1-2days
• Prednisolone 1-4mg/kg/day
• IV anti-D therapy(50-75microg/kg)
• IVH-platelet transfusion,IVIG,high-dose corticosteroids
• Splenectomy-
• ≥4yr,severe ITP,>1yr
• Not easily controlled with therapy
• ICH
12. Secondary to SLE/HIV
• When the onset is insidious, especially in an adolescent, the
possibility of a systemic illness, such as systemic lupus
erythematosus (SLE), is more likely.
• HIV-associated ITP is usually chronic
13. Drug-induced
thrombocytopenia
• Result of either an immune process/megakaryocyte injury
• Valproic acid, phenytoin, carbamazepine, sulfonamides,
vancomycin, and trimethoprim-sulfamethoxazole
• Heparin-induced thrombocytopenia occurs after exposure to
heparin, the patient has an antibody directed against the
heparin–platelet factor 4 complex.
14. Maternal ITP
• Have lower risk of serious hemorrhage
• Treatment
• prenatal administration of corticosteroids to the mother
• administration of IVIG
• sometimes corticosteroids to the infant after delivery
• Usually resolves within 2-4months after delivery
15. Neonatal alloimmune
thrombocytopenic purpura
• Development of maternal antibodies against antigens present
on fetal platelets that are shared with the father
• 1 in 4000-5000 live births
• C/F-apparently well child -generalised petechiae and purpura
within 1st few days
• 30% may have ICH
• Diagnosis-presence of maternal alloantibodies directed
against the father’s platelets
• Treatment -administration of IVIG prenatally to the mother
from 2nd trimester throughout pregnancy
16. Type 2B VWD
• Results from mutations that increase the ability of VWF to
bind platelets.
• This leads to increased clearance of both VWF and platelets
from circulation and results in decreased VWF activity
• Diagnosis-direct measurement of the increased platelet
binding/increased response to low-dose ristocetin on platelet
aggregation testing.
• Thrombocytopenia is not always present and may be more
prominent during times of stress such as surgery or
pregnancy.
17. Platelet-type VWD
• Mutation in platelet GPIb causes spontaneous binding to VWF
• Presents with decreased VWF activity, loss of high-molecular-
weight multimers, and thrombocytopenia similar to type 2B
VWD.
• Treatment-platelet transfusion
18.
19. Thrombocytopenia-absent
radius syndrome
• Thrombocytopenia (absence or hypoplasia of megakaryocytes)
that presents in early infancy
• Bilateral radial anomalies of variable severity, ranging from
mild changes to marked limb shortening
20.
21. Wiskott-aldrich syndrome
• Characterized by eczema, and recurrent infection as a
consequence of immune deficiency.
• It is inherited as an X-linked disorder.
• Splenectomy often corrects the thrombocytopenia
X-linked thrombocytopenia
• point mutation within the WAS gene
22. Congenital amegakaryocytic
thrombocytopenia
• Manifests within the 1st few days to week of life
• Child presents with petechiae and purpura caused by profound
thrombocytopenia.
• A rare defect in hematopoiesis as a result of a mutation in the stem
cell TPO receptor.
• Bone marrow shows an absence of megakaryocytes.
• Often progress to marrow failure (aplasia) over time.
• Hematopoietic stem cell transplantation is curative
23.
24. Microangiopathy
• DIC,HUS,TTP
• RBC destruction and consumptive thrombocytopenia due to
platelet and fibrin deposition in the microvasculature
• Presence of RBC fragments including helmet
cells,schistocytes,spherocytes and burr cells
25. Hemolytic uremic syndrome
• It is a common cause of community acquired AKI
• Triad-microangiopathic hemolytic anemia,
thrombocytopenia, and renal insufficiency
• Most common - toxin-producing Escherichia coli that
causes prodromal acute enteritis (diarrhea-associated
HUS)
• Asia,southern Africa-Shigella dysenteriae type 1
• Western countries-verotoxin or Shiga-like toxin producing
E. coli (STEC)
• Genetic –deficiencies of vWF cleaving
protease/complement factor H, I, or B, and defects in
vitamin B12 metabolism(absence of preceding diarrhea
prodrome)
27. • Treatment
• prompt correction of volume deficit
• control of hypertension
• early institution of dialysis
28. Thrombotic thrombocytopenic
purpura
• Pentad of
• Fever
• Microangiopathic hemolytic anemia
• Thrombocytopenia
• Abnormal renal function
• Central nervous system changes
• Microvascular thrombi within the central nervous system
cause subtle neurologic signs
• Initial manifestations are often nonspecific
• Diagnosis-microangiopathic hemolytic anemia characterized
by morphologically abnormal RBCs, with schistocytes,
spherocytes, helmet cells, elevated reticulocyte count
29. • Treatment-plasmapheresis (effective in 80-95% of cases)
based on thrombocytopenia and microangiopathic hemolytic
anemia
• Rituximab, corticosteroids, and splenectomy are reserved for
refractory cases.
• The majority of cases of TTP are caused by an autoantibody–
mediated deficiency of a metalloproteinase (ADAMTS-13) that
is responsible for cleaving the high-molecular-weight
multimers of VWF
• ADAMTS- 13 deficiency can be treated by repeated infusions
of fresh-frozen plasma.
30.
31. Sequestration
• Thrombocytopenia develops in individuals with massive
splenomegaly because the spleen acts as a sponge for
platelets and sequesters large numbers.
• Most such patients also have mild leukopenia and anemia on
CBC.
• Individuals who have thrombocytopenia caused by splenic
sequestration should be diagnosed for etiology of
splenomegaly, including infections, inflammatory, infiltrative,
neoplastic, obstructive, and hemolytic causes.
32. Kasabach –Merritt syndrome
• The association of a giant hemangioma with localized
intravascular coagulation causing thrombocytopenia and
hypofibrinogenemia
• In most patients, the site of the hemangioma is obvious, but
retroperitoneal and intraabdominal hemangiomas may
require body imaging for detection.
• Inside the hemangioma there is platelet trapping and
activation of coagulation, with fibrinogen consumption and
generation of fibrinogen degradation products.
33.
34. Thrombocytopenia from
acquired disorders
• Infiltrative disorders like malignancies(ALL),histiocytosis,
lymphomas, and storage disease
• Aplastic processes may present as isolated thrombocytopenia
or along with leukopenia, neutropenia, anemia, or
macrocytosis
• Bone marrow examination should be performed when
thrombocytopenia is associated with abnormalities found on
physical examination or on examination of the other blood cell
lines.
35. Thrombocytosis
• Increased platelet count above normal >4 lakhs
• Primary
• Myeloproliferative disorders
• Essential thrombocythemia,PCV,CML,idiopathic myelofibrosis
• Leucocytosis,immature white cells,nucleated red cells,defective
platelet function,splenomegaly
• Secondary
• Hemorrhage ,trauma ,infections ,iron deficiency ,malignancy ,
splenectomy ,chronic inflammatory disease
• Features of underlying causative disorder are evident
