1. MODERATOR:-
DR. ALPIKA SHUKLA
(ASSOCIATE PROFESSOR OF MEDICINE)
GSVM MEDICAL COLLEGE
PRESENTED BY:-
SOUBHAGYA RANJAN DAS
JR-1 MEDICINE
APPROACH TO
THROMBOCYTOPENIA
2. NORMAL PHYSIOLOGY OF PLATELETS
Platelets are normally made in the bone marrow from progenitor
cells known as megakaryocytes.
Normal platelet lifespan is 10days & everyday 1/10th platelet pool
is replenished.
Normal platelet count is 150,000-450,000/ mm³
Contain intracellular granules (alpha and delta) that contain
coagulation factors and ADP.
Production stimulated by thrombopoietin from liver/kidney.
3. Reticulated platelets
The youngest platelets in the circulation contain RNA and
called as Reticulated platelets or the immature platelet
fractions(IPF).
Measurement of the percentage of reticulated platelets
identifies platelets that have recently been
released from the bone marrow .
Normal subjects :- 1.3%
There is an increased percentage of reticulated platelets in
patients with thrombocytopenia caused by increased
destruction .
A normal to reduced percentage of reticulated platelets in
patients with deficient production.
4. THROMBOCYTOPENIA
Thrombocytopenia may be defined as a subnormal
number of platelets in the circulating blood.
Normal platelet count :- 150,000-
450,000/microlitre
It is the most common cause of abnormal bleeding.
5. How low is too low?
150,000-50,000:- No symptoms
50,000-20,000:- first symptoms appear
20,000-10,000:- potentially life threatening.
<10,000:- spontaneous intracranial hemorrhage.
12. 4. Abnormal platelet distribution or
pooling:-
- Disorders of the spleen (neoplastic, congestive,
infiltrative, infectious, of unknown cause)
-Hypothermia
-Dilution of platelets with massive transfusions
13. Approach
1. History :-
Onset(new/chronic/relapsing)
Recent medication and vaccination
Recent transfusion(hemodilution)
Recent organ transplant
Autoimmune disease/malignancy
Pregnancy
Travel history(malaria,rickettsia,dengue)
Dietary habit(megaloblastic anemia)
Ingeston of alcohol/quinine containing beverages
14. 2. Clinical Examination:-
a. Look for petechiae,purpura or superficial
bleeding.
b. Joint or soft tissue bleeding-DIC
c. Ischemic limb/skin necrosis-HIT
d. Examine for hepatosplenomegaly and
lymphadenopathies
e. Presence of retinal hemorrhage on occular fundus
examination is a predictor of CNS hemorrhage
16. IMMUNE THROMBOCYTOPENIA
The syndrome of ITP is caused by platelet-specific
autoantibodies that bind to autologous platelets, which are
then rapidly cleared from the circulation by the
mononuclear phagocyte system via macrophage Fcγ
receptors predominantly in the spleen and liver.
1. Primary:-It refers to thrombocytopenia in which apparent
exogenous etiologic factors are lacking and in which diseases
known to be associated with secondary thrombocytopenia have been
excluded
2.Secondary:-If associated with other underlying causes.
17. features Acute ITP Chronic ITP
Peak age of incidence Children, 2-6 y Adults, 20-40 y
Sex predilection None 3:1 female to male
Antecedent infection Common 1-3 wk before Unusual
Onset of bleeding Abrupt Insidious
Hemorrhagic bullae in mouth Present in severe cases Usually absent
Platelet count <20,000/µl 30,000-80,000/µl
Eosinophilia and lymphocytosis Common Rare
Duration 2-6 wk; rarely longer Months or years
Spontaneous remissions Occur in 80% of cases Uncommon
18. History
Findings Disorder of platelets Disorder of coagulation
Petechia Characteristic Rare
Deep dissecting
hematomas
Rare Characteristics
Superficial ecchymoses Characteristics Common
Hemarthrosis Rare Characeristic
Delayed bleeding Rare Common
Bleeding from superficial
cuts and scratches
Persistent : often profuse Minimal
Sex of patient Relately more common in
females
80-90% in males
Positive family history Rare(except vWD &
hereditary hemorrhagic
telengectesia)
common
19. Clinical manisfestations
Bleeding
- Petechiae
- Purpura: Dry(cutaneous) or wet(mucosal bleed)
-Epistaxis
-Severe hemorrhage: ICH, UGI bleed, Menorrhagia
20. Diagnosis
The diagnosis of ITP is usually a diagnosis of exclusion based on
a demonstration of peripheral thrombocytopenia, with a history,
physical examination, and complete blood count that do not
suggest another cause for the thrombocytopenia.
Laboratory testing is performed to evaluate for secondary causes
of ITP and should include testing for HIV infection and hepatitis
C (and other infections if indicated). Serologic testing for SLE,
serum protein electrophoresis, immunoglobulin levels to
potentially detect hypogammaglobulinemia, selective testing for
IgA deficiency or monoclonal gammopathies, and testing for H.
pylori infection should be considered, depending on the clinical
circumstance. If anemia is present, direct antiglobulin testing
(Coombs’ test) should be performed to rule out combined
autoimmune hemolytic anemia with ITP (Evans’ syndrome)
21. Treatment
New
diagnosis of
ITP
Platelet count> 20-30000/µL
No treatment in the absence of special
circumstances
Inital treatment for plt count <20,000/µL
Prednisone(1mg/kg/d) or dexa(40mg/day x 4days)
±IV anti-D(µg/kg)
±IVIG(1g/kg/day x 1-2days)
Treatment for refractory thrombocytopenia
<20,000/µL
Splenectomy
Thrombopoeitin mimetics
-Eltrombopag(50mg/kg)
-Romiplostim(1-10mcg/kg SC
weekly)
Rituximab (375mg/m² IV weekly x 4wk)
Stable patient count >30-50,000/µL
No therapy, observe
22. Emergency
-IV methylpred(1g/day) x 3days
+
-IVIG(1g/kg/d) x 1-2days
±anti-D(50-75µg/kg)
±IV vincristine(1-2mg)
±platelet transfusion
±factor VIIa
23. SPLENECTOMY
INDICATION:- Failed corticosteroid therapy.
Single best option to convert a patient with ITP into
“non-patient”.
Approximately 85% patient attain a hemostatic
response after splenectomy.
Immunize with polyvalent pneumococcal, H.
Infleunza type-B and meningococal polysachharide
vaccine atleast 2wk prior to splenectomy if possible.
25. Thrombotic Thromocytopenic Purpura
An inherited or acquired defciency(due to
autoantibodies) of von Willebrandfactor-cleaving
protease known as ADAMTS13.
Leads to accumulation of large multimer of VWF which
cause spontaneous platelet aggregation or thrombi.
Can be induced by drugs.
Increased incidence with pregnancy or HIV>
26. TTP- Diagnostic features
*Microangiopathic Hemolytic
Anemia(MAHA)
-Elevated LDH, elevated bilirubin
-schistocytes on peripheral
smear(MUST BE PRESENT)
*Low platelet(MUST BE PRESENT)
*fever
*Neurologic symptoms:-
headache,sleepiness,confusion,
stupor,stroke,coma,seizures.
*Renal manifestations:-
hematuria,protienuria elevated
creatinine,BUN
*CBC normal or slightly elevate
WBC
*Hb is moderately decreased 8-9
g/dL
*Platelet ranges from 20,000-
50,000
*RBC are fragmented and appears
as schistocytes
*Decreased Haptoglobin
*Increased Reticulocyte count
*Negative direct anti globulin test
27. Treatment
Therapeutic plasma exchange (TPE) remains the
mainstay of treatment of TTP. TPE is continued until
the platelet count is normal and signs of hemolysis
are resolved for at least 2 days.
Plasma infusion is used as an emergent substitute
until plasma exchange is available.
Addition of rituximab to initial therapy decreases
duration of TPE and relapses.
28. Hemolytic Uremic Syndrome(HUS)
HUS is a syndrome characterized by:-
1. Acute renal failure
2. Microangiopathic hemolytic anemia
3. Thrombocytopenia
-Predominantly affects children.
-TYPES:-
a.Typical HUS
b. Atypical HUS
c.HUS due to complement abnormalities.
29. Typical/Diarrhea associated/Shiga toxin associated
HUS:-
Enterohaemorrhagic E.coli
Shigella dysenteria type-I
Common serotype of E.coli:o157:H7
Sources of infection are:
- Milk & animal products
- Human feco-oral transmission
30. Atypical/Non-Diarrhea related HUS
Pnuemococcal HUS
HUS due to complement abnormalities
Miscellaneous causes of HUS/TTP
-Abnormalities in intracllular vit.B12 metabolism
-HIV
-SLE
-Malignancies
-Radiation
-Certain Drugs
31. Other infections associated with HUS:-
-Influenza
-CMV
-Infectious mononucleosis
-Salmonella
-streptococcus
32. Diagnosis
Clinically,HUS can be very difficult to distinguish from TTP.
features TTP HUS
Age Adult Children <5yr
MAHA Present Present
Thrombocytopenia Present Present
Fever Present Absent
Severe renal failure Uncommon Common
Major neurological
abnormalities
Common Uncommon
Prodrome bloody diarrhea Absent Present (typical HUS)
Cause Severe deficiency of
ADAMTS13
Infection by E.coli
O157:H7
Coagulation test Normal Normal
Treatment Plasma exchange Supportive
33. Treatment
Treatment of HUS is primarily supportive.
In patients with aHUS, eculizumab, a humanized
monoclonal antibody against C5 that blocks terminal
complement, has efficacy in resolution of aHUS and
improving or preserving renal function.
34. Heparin Induced Thrombocytopenia
HIT, also known as the white clot syndrome, is increasingly recognized
as a potentially severe, albeit paradoxical, immune-mediated
complication of heparin therapy.
Drug-induced thrombocytopenia due to heparin differs from that seen
with other drugs in two major ways:-
1. The thrombocytopenia is not usually severe, with nadir counts rarely
<20,000/µL.
2. Heparin-induced thrombocytopenia (HIT) is not associated with
bleeding and, in fact, markedly increases the risk of thrombosis.
Mechanism of thrombocytopenia:-Antibody formation to a complex of
the PF4 and Heparin.
35. Diagnosis
4 T’s in diagnosis of HIT:-
a.Thrombocytopenia(rarely 20,000)
b.Timing of platelet drop: witin 5-14 days of heparin
exposure
c.Thrombosis
d.other causes of Thrombocytopenia ruled out
36. Treatment
The initial treatment of HIT with or without thrombosis is
to discontinue all exposure to heparin or LMWHs
(including heparin-coated catheters) and immediately
begin an alternative anticoagulant, usually a DTI, such as
argatroban, lepirudin, or bivalirudin).
Consider anticoagulation even in absence of thrombosis.
If thrombosis present: warfarin for 3month, started only
with overlap of DTI or Fondaparinux and after resolution
of thrombocytopenia.
