2. Definitions
Stages of platelets Developement
Causes
Approach to Thrombocytopenic Patient
Diagnosis
Treatment
3. Thrombocytopenia is defined as an count
less than 150000/mm₃
Pseudothrombocytopenia –Blood collected
in EDTA tube leads to platelets clumping due
to the presence of antibodies usually IgG but
also IgM IgA
4.
5. Decreased Production
Hematologic malignancies
Aplastic anemia
Myelodysplasia
Drugs: chemotherapy, alcohol
Radiation
HIV
Hereditary thrombocytopenias
Metastatic cancer to bone marrow
7. Histoty
usually asymptomatic
Presence of petechiae, ecchymoses
Mucocutaneous bleeding
Purpura
Rarely central nervous system bleeding
retinal hemorrhages
8. History of…
Recent Infections
Malignancies
Pregnancy status in premenopausal woman
Recent medications
Vaccinations
Recent travels
Recent transfusions
Recent organ transplantation
Family history of thrombocytopenia
Autoimmune disorders
9. presence of petechiae ecchymosis in the skin,
wet purpura in mucous membranes
Splenomegaly
The presence of retinal hemorrhage on ocular
fundus examination is a predictor of CNS
hemorrhage
12. Due to the presence of naturally occurring
antibodies that cross-react with the drug bound
to the platelet.
The thrombocytopenia occurs after a period of
initial exposure of 21 days
Resolves in 7–10 days after drug withdrawal.
Abciximab exposure causes thrombocytopenia
within 24 h of initial exposure.
14. The thrombocytopenia is not usually severe,
rarely <20,000/μL.
Heparin-induced thrombocytopenia (HIT) is
not associated with bleeding, it increases the
risk of thrombosis.
Antibodies to complex of platelet factor 4
and heparin
HIT after exposure to heparin for 5–14 days.
15.
16. HIT (anti-heparin/PF4) antibodies can be
detected using two types of assays.
The most widely available is an enzyme-linked
immunoassay (ELISA).
The other assay is a platelet activation assay,
most commonly the serotonin release assay,
17. Direct thrombin inhibitor (DTI)
- Argatroban
-Fondaparinux
Xa Inhibitor-Danaparoid
Warfarin therapy.
18. Immune thrombocytopenic purpura (ITP); is an
acquired disorder
It is immune-mediated destruction of platelets
and inhibition of platelet release from the
megakaryocyte.
In children, it is usually an acute disease.
In adults, it is a more chronic disease.
Secondary ITP if it is associated with an
underlying disorder;
autoimmune disorders, particularly systemic
lupus erythematosus (SLE),
infections, such as HIV and hepatitis C.
19. ITP is characterized by mucocutaneous
bleeding and a low, often very low platelet
count, with an otherwise normal peripheral
blood cells and smear.
Patients usually present either with
ecchymoses and petechiae.
Mucocutaneous bleeding may be present.
Rarely, life-threatening, including central
nervous system bleeding can occur.
retinal hemorrhages
20. prednisone at 1 mg/kg,
Anti Rh0(D) immune globulin at 50–75
μg/kg,
Monitoring patients for 8 h after infusion
Intravenous gamma globulin (IVIgG)
splenectomy
Eltrombopag is FDA approved for use in children
over 1 year of age.
Romiplostim is not yet FDA approved in children
but a randomized trial supports efficacy.
Immunosuppressive drugs- mycophenolate mofetil
dapsone.
21. TTP is related to a deficiency or antibodies
to the metalloprotease ADAMTS13, which
cleaves VWF.
ADAMTS13 activity levels of <10% are more
clearly associated with antibody-mediated
TTP.
Idiopathic TTP appears to be more common
in women than in men.
24. HUS is a syndrome characterized
1) Acute renal failure
2) Microangiopathic hemolytic anemia,
3) Thrombocytopenia.
Escherichia coli O157:H7 is the most frequent
causative agent
Atypical HUS (aHUS) is usually due to genetic
defects that result in chronic complement
activation or antibodies directed against
complement regulatory proteins.
25. Indications of platelets tranfusion
10,000/uL - prophylactic transfusion
20,000/uL - in the presence of bleeding,
fever, infection, platelet function defect, or
coagulopathy
50,000/uL - prior to minor procedures, in
actively anticoagulated patients or in the
presence of active bleeding
75,000/uL - prior to general surgery
100,000/uL - prior to neurologic or
ophthalmologic surgery
27. Thrombocytopenia if platletes <150000/ul
then Pseudothrombocytopenia should be
ruled out
Proper history taking and examination for
finding out of different causes
Peripheral blood smear to find out causes
Indications of platelets transfusion
<10000/ul
pseudothrombocytopenia,” particularly in a patient without an apparent cause for the thrombocytopenia. Pseudothrombocytopenia (Fig. 111-1B) is an in vitro artifact resulting from platelet agglutination via antibodies (usually IgG, but also IgM and IgA) when the calcium content is decreased by blood collection in ethylenediamine tetraacetic (EDTA) (the anticoagulant present in tubes
collect blood for complete blood counts [CBCs]). If a low platelet count is obtained in EDTA-anticoagulated blood, a blood smear should be evaluated and a platelet count determined in blood collected into sodium citrate (blue top tube) or heparin (green top tube), or a smear of freshly obtained unanticoagulated blood, such as from a finger stick, can be examined
Mucocutaneous bleeding
such as oral mucosa, gastrointestinal, or heavy menstrual bleeding, may be present
Wet purpura (blood blisters in the mouth) and retinal hemorrhages may herald life-threatening bleeding.
Petechiae size <4 mm
Petechiae are pinpoint, nonblanching hemorrhages and are usually a sign of a decreased platelet number and not platelet dysfunction.
Echymosis flat blue or purple patch size about >1 cm
Purpura small small purple spots size 4-10 mm
Medical history can provide invaluable information and greatly facilitate diagnosis. Aspects of particular relevance that should be investigated include
Congenital thrombocytopenia
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 (Fig. 111-1C). 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 Gp Ib-IX-V, the VWF adhesion receptor. X-linked disorders include Wiskott-Aldrich syndrome
recent travels (eg, malaria, rickettsiosis, dengue fever);
Recent transfusions; alloimmune Thrombocytopenia
Splenomegaly exclude any chronic liver ds, leukemia lymphoma other hematological malignancy
Now I m going to discuss some important cause of thrombocytopenia one by one in brief
HIT can occur after exposure to low-molecular-weight heparin (LMWH) as well as unfractionated heparin (UFH),it is more common with UFH
HIT results from antibody formation to a complex of the platelet-specific protein platelet factor 4 (PF4) and heparin. The anti-heparin/PF4 antibody can activate platelets through the FcγRIIa receptor and also activate monocytes and endothelial cells. It occurs before 5 days in those who were exposed to heparin in the prior few weeks or months (<~100 days)
Because many patients develop antibodies but do not develop clinical HIT, the test has a low specificity for the diagnosis of HIT. This is especially true in patients who have undergone cardiopulmonary bypass surgery, where ∼50% of patients develop these antibodies postoperatively. IgG-specific ELISAs increase specificity but may decrease sensitivity.
which measures the ability of the patient’s serum to activate platelets in the presence of heparin in a concentration-dependent manner. This test has lower sensitivity but higher specificity than the ELISA. However, HIT remains a clinical diagnosis
Warfarin if started, should be overlapped with a DTI or fondaparinux and started after resolution of the thrombocytopenia and lessening of the prothrombotic state
(ITP; also termed idiopathic thrombocytopenic purpura)
Childs most commonly following an infection, and with a self-limited course
although in some adults, spontaneous remission occurs, usually within months of diagnosis
Viruses like CMV,Infectious mononucleosis VZV,
TUBECULOSIS
H pylori
Mucocutaneous bleeding such as oral mucosa, gastrointestinal, or heavy menstrual bleeding
Eltrombopag oral
s/e hepatotoxicity
Romiplostim i/v in week
TTP is related to a deficiency of, or antibodies to, the metalloprotease ADAMTS13, which cleaves VWF. which are then cleaved by ADAMTS13. The persistence of ultra-large VWF molecules is thought to contribute to pathogenic platelet adhesion and aggregation
Laboratory testing for DNA variants in complement regulatory genes is available, although assigning pathogenicity to variants remains challenging. Currently there is not a functional assay that is diagnostic of the disease.
It is seen preceded by an episode of diarrhea, often hemorrhagic in nature, predominantly in children.
1 unit RDP increases plts 5-8 thousands
1 units of SDP increases 30-50 thousands
