Presentation is about THROMBOTIC THROMBOCYTOPENIC PURPURA.

1. THROMBOTIC THROMBOCYTOPENIC PURPURA
Presented by:
Dr. Madiha Bashir
(PGY-1 MEDICINE)

2. Outline
1. Case Report
2. History
3. Examination
4. Differential Diagnosis
5. Treatment

3. 1. Case Report
A 32-year-old woman comes to the ER complaining of episodic
frontal headache, difficulty moving her tongue, difficulty speaking, and
intermittent numbness of her extremities for the last week.

4. History
History of presenting complaints: Patient developed intermittent frontal headache
that was not associated with photophobia, increased lacrimation or sneezing. There was
difficulty moving her tongue, difficulty speaking, and intermittent numbness of her
extremities for the last week, there was no associated neck stiffness, dizziness, loss of
consciousness fits, or discoloration of extremities.
Past medical and surgical history: Insignificant

5. Examination
● well oriented in time, place and person.
● VITALS: BP: 130/80, HR: 90/min, RR: 15/min, temp100 °F
● GENRAL PHYSICAL EXAMINATION: there was pallor, no other significant findings.
● Systemic Examination: There was no significant findings with no focal deficit.

6. INVESTIGATIONS

7. CBC
Test Patient Result Normal Value
WBC 7.1 4.8-10
HEMOGLOBIN 7.4 12-16
HEMATOCRIT 24 37-47
MCV 86 78-96
RBC 2.9 4.2-5.4
PLATELET COUNT 38 180-400
RDW 21 ---

8. Electrolytes, Creatinine, Glucose

9. Liver Function Tests

10. Test Patient Result Normal Value
PT 11 seconds 10-13 seconds
PTT 28 seconds 26- 36 seconds
Fibrinogen 199 mg/DL 200-400 mg/DL
D-dimer <0.5 mg/ml 0- 0.5 mg/ml
Coagulation Screening Tests

11. Cardiac Enzymes: normal
Hepatitis serology: non-reactive
Blood Cultures: This patient has a temperature of 100 °F without any localizing
signs. DIC and sepsis might cause thrombocytopenia, so obtaining several blood
cultures early in the hospitalization is not inappropriate.
Patient Result: No growth at 48 hours
Reticulocyte count: 8.5% (normal 0.5-1.5%);
Coomb's Test: Negative Direct and Indirect. (to rule out autoimmune hemolytic
anemia).
Peripheral film: The peripheral blood smear revealed thrombocytopenia and the
presence of schistocytes.
ANA: negative
CT scan Brain: No acute hemorrhage or infarct.

13. Most striking laboratory test findings?
Low hemoglobin and hematocrit, low platelet
count, elevated LDH, and unconjugated
hyperbilirubinemia with schistocytes on
peripheral film,
suggests???
Microangiopathic hemolysis with thrombocytopenia.

14. MAHA
• nonimmune hemolysis (negative coombs) with prominent
red cell fragmentation (schistocytes) on peripheral blood
smear. Will exhibit increased LDH and indirect bilirubin.
Schistocytes
• in the appropriate clinical setting schistocyte count>1%
was strongly suggestive of TTP-HUS, ie 2 or more schistos
in microscopic field at 100x magnification.

16. Differential Diagnosis
1. HUS
● diarrhoeal prodromes
● more severe and persistent symptoms of renal impairment.
● difficult to distinguish TTP from atypical HUS, except for the paradigmatic
prevalence of neurological symptoms in the former and of renal failure in the latter .
2. DIC
● markedly increased levels of fibrin degradation
● products and D-dimer and, in decompensated cases, by the presence of
hypofibrinogenaemia and prolonged PT, APTT

17. Differential Diagnosis
Malignant hypertension is less frequent, renal damage is not as severe
and the degrees of anaemia and thrombocytopenia are more severe in
TTP.
HELLP syndrome (haemolysis, elevated liver enzymes and low
platelets) Abnormally high serum transaminases
Connective tissue disorders (systemic lupus erythematosus and
severe scleroderma) symptoms and signs are usually less severe, and
laboratory tests such as antinuclear antibodies and lupus - like
anticoagulant give positive results.

18. Differential Diagnosis
4. Evans syndrome positive Coombs test, lack of schistocytes and the usual
absence of end - organ ischaemic symptoms.
5. Disseminated malignancy Until further investigations exclude or confirm the
presence of metastatic cancer, it is not easy to distinguish TTP from this type of
TMA.

19. Thrombotic thrombocytopenic
purpura
The Classic Pentad of TTP
● Microangiopathic hemolytic anemia
● Thrombocytopenia
● Renal insufficiency or abnormalities
● Neurologic abnormalities that can be fluctuating
● Fever
● the latter 3 (ie, renal dysfunction, fever, and
neurological signs and symptoms) are not present
consistently.

20. Etiology
Normally a protease known as ADAMTS13 (A disintegrin and
metalloprotease with thrombospondin type 1 repeats, member 13) is
responsible for cleaving von Willebrand multimers and preventing the
aggregation of von Willebrand factor and subsequent platelet activation
and hyperadhesion.
Thrombotic thrombocytopenic purpura is caused by an acquired or
congenital deficiency in ADAMTS13 activity which produces inappropriate
platelet clumping leading to thrombocytopenia. Destruction of red blood
cells by these platelet clumps produces hemolytic anemia and embolization
of these aggregates produces embolic events.

23. Investigations

24. Investigations

25. Investigations

27. TREATMENT OF TTP

28. 1. PLASMA EXCHANGE:
The mortality rate for untreated TTP/HUS is almost 90%. Prompt institution of plasma
exchange is the treatment of choice.
● the first session of plasmapheresis consists of exchanges (1.5 to 2 volumes) with
FFP, 24-hour plasma, or thawed plasma, while subsequent daily sessions, at
least 12 hours apart, exchange 1.5 volumes.
● This regimen is continued until the platelet count and LDH level is normal , and
then the patient is switched to 1- volume-per-day exchanges for 3 to 4 days. If
the platelet count and LD level remain stable over the next 3 to 4 days, plasma
exchange may be discontinued. Response to this therapy is usually seen after 5
to 6 sessions.

29. 2. Corticosteroids
● Intravenous daily methylprednisolone (e.g. 1 g/d for three consecutive days –
adult dose) or high dose oral prednisolone (e.g. 1 mg/kg/d) should be
considered.
3. Rituximab
● In acute idiopathic TTP with neurological/cardiac pathology, which are
associated with a high mortality, rituximab should be considered on
admission, in conjunction with PEX and steroids.
● Patients with refractory or relapsing immune-mediated TTP should be offered
rituximab.

30. 4. Cyclosporin
● A Recommendation CSA may be considered as second line therapy in patients
with acute or chronic relapsing acquired TTP.
5. Splenectomy. Splenectomy may rarely be considered in the non-acute period of
immune-mediated TTP but has limited proven benefit.
6. Supportive therapy Red cell transfusion should be administered according to
clinical need especially if there is cardiac involvement (1A).
● Folate supplementation is required during active haemolysis (1A).
● Platelet transfusions are contra-indicated in TTP unless there is life-threatening
haemorrhage (1A).

31. ● Platelet transfusions are contra-indicated in TTP unless there is life-
threatening haemorrhage.
● Thromboprophylaxis with LMWH is recommended once platelet count has
reached >50 3 109/l .
Response
According to the 2012 American Society of Apheresis Consensus Conference on
TTP, response is defined as achieving a platelet count >150 000/μL for 2
consecutive days, a normal or near normal lactate dehydrogenase (LDH), and
stable or improving neurologic deficits

32. Refractory TTP is defined as a failure of platelet response after 4 to 7 days of
PEX, or a clinical deterioration in a patient receiving standard therapy.
● Increased frequency of PEX and addition of rituximab can be considered
in refractory TTP .

33. THANK YOU