Clinical profile of cardiomyopathy in western India: A study over 2 years

1. Dr. Sachin Adukia, Post graduate student, Bharati hospital and research center, Pune.

2.  An 18 year old, previously healthy, primigravida of 26
weeks gestation.
 Admitted late night with complaints of
 mild fronto-temporal throbbing headache
 scanty clear vomit x 2 days
 low grade fever.
 Early morning she had
 an episode of generalized tonic clonic seizure lasting 2 to 3 mins
 followed by loss of consciousness.

3. Physical examination
 Her blood pressure remained 170/110 mm Hg inspite of
giving nifedipine and alpha-methyldopa.
 Both pupils were equal, reacting to light; bilateral
plantars extensor.
 Mild Pallor +
 Other systems were normal.

4. Initial diagnosis and Investigations
Result
Negative ANA Test
Normal venogram but MRI s/o
PRES
Investigations ordered
Antinuclear antibody test MRI brain with venogram
Initial differential diagnosis
Systemic lupus erythematosus Central venous sinus thrombosis

5. MRI Brain s/o PRES and Normal Venogram

6. Primary investigations (1)
 Hemogram: severe hemolysis with thrombocytopenia.
Peripheral blood smear
showing severe
hemolysis.
1. microcyte
2. horn cell (keratocyte)
3. macrocyte
4. microspherocyte
5. schistocytes
6. polychromatin cell

7. Primary investigations (1) [..contd]
Investigation Day 1 Day 3 Day 5
Hemoglobin 9.9 6.6 7.6
Total leucocytic count 22,800 18,400 28,300
Differential count Neutrophils 87%
Lymphocytes 7%
Neutrophils 75%
Lymphocytes 19%
Neutrophils 72%
Lymphocytes 24%
Platelets 50,000 10,000 Day 5 -30,000
Urea 35
Creatinine 1.2
Bilirubin (direct/indirect) 0.5/1.1
Aspartate transaminase 484
Alanine transaminase 311
Lactate dehydrogenase 4687

8. Other investigations (2)
 Urine examination:
 Dark red turbid urine
 RBC’s plenty s/o haemoglobinuria,
 sugar and protein absent.

9. Other investigations (3)
 USG abdomen:
 Single live intra-uterine pregnancy- 25 weeks 6 days with
oligohydramnios
 asymmetric intra uterine growth retardation.
 Medical termination of pregnancy done;
 procedure uneventful

10. severe
hemolysis
fever
bleeding
multiorgan
involvement
thrombocyto
-penia Sepsis
vs.
DIC

11. Blood culture and
urine culture:
No growth
Normal DIC screen
Sr. Fibrinogen 344
D-dimer Negative
PT 19.5
APTT 27.9
HELLP Syndrome Thrombotic
microangiopathy
Sepsis
DIC

12. HELLP vs. Thrombotic Thrombocytopenic Purpura
Feature TTP HELLP
Neurological features
Fever
Hypertension
Renal dysfunction
Purpura with bleeding
Platelets
PT/APTT
Fibrinogen
BUN/Creatinine
Liver enzymes
LDH
+++
+++
±
±
++
Markedly reduced
Normal
Normal
Increased
±
Markedly Increased
±
-
±
±
-
Reduced
Prolonged
Reduced
Increased
+
Can be increased

13. The Classic Pentad: Diagnosis established!!!

14. Treatment: Pre- and Post-diagnosis
Pre
• IV Antibiotics and IV Steroids
• Packed red cells and Platelets
• Supportive treatment
Post
• Plasmapheresis
• Fresh frozen plasma
• Above treatment continued

15. Clinical course and Outcome
 She underwent a total of 5 sittings of plasmapheresis
(therapeutic plasma exchange) with fresh frozen plasma (FFP).
 She continued to receive packed red cells and platelet
transfusions.
 4 FFPs were transfused daily till platelet and LDH
normalization.
 Urine output improved as did the RFT’s
 No repeat convulsions, neurologically improved; weaned off
ventilatory support completely.
 Once stable, she was discharged on day 12.

16.  Thrombotic thrombocytopenic purpura (Moschcowitz syndrome)-
1925

17. Thrombotic thrombocytopenic purpura in pregnancy
 Classified as idiopathic, secondary (65%) and familial
 TTP has a strong relation to pregnancy
 seen as commonly as 1 in 25,000 pregnancies.
 Reason
 association of pregnancy with increasing concentrations of
procoagulant factors
 decreasing fibrinolytic activity
 loss of endothelial cell thrombomodulin
 decreasing activity of ADAMTS-13.
 All of these abnormalities worsen through the course of
pregnancy until delivery and immediately post-partum.

18. Pregnancy-associated microangiopathies
Entity MAHA Thrombocytopenia Coagulopathy High BP Abdominal
symptoms
Renal
Impairment
Neurological
symptoms
Pre
Eclampsia
+ + +/- +++ +/- +/- ++
HELLP + ++ +/- + +++ + +/-
TTP ++ +++ - +/- + ++ +++
HUS + ++ +/- ++ + +++ +/-
SLE + + +/- + +/- ++ +
Delivery generally leads to a rapid resolution of preeclampsia and HELLP
syndrome, however if no improvement is seen after 48 to 72 hours of
delivery, possibility of thrombotic microangiopathies should be considered.

19. Posterior reversible encephalopathy syndrome in TTP
 Posterior reversible encephalopathy syndrome (PRES)
 the predominant brain neuroimaging abnormality in TTP.
 no association between degree of hypertension, hematocrit or
platelet count, D dimer, fibrinogen, LDH, or total bilirubin levels
and PRES.
 The presentation:
 Benign- headache, vomiting
 Severe- confusion, seizures, visual abnormalities and motor signs.
 is completely reversible if the underlying cause is treated early
 However, PRES in TTP is associated with worse renal
function.

20. Mortality in TTP in pregnancy
• widespread microvascular thromboses
• multiple organ dysfunction
Maternal
Mortality
• Placental infarction leads to fetal
intra-uterine growth retardation
and/or mortality
Fetal
mortality

21. Treatment modalities

22. Plasmapheresis: a boon of modern science
•Plasmapheresis
(therapeutic plasma
exchange- TPE) has
reduced mortality
rates, from over
90% to 10–20%.
•Earlier initiation of
TPE correlates with
a better prognosis.
• TPE allows
removal of
autoantibody, and
repletes ADAMTS13.

23. The prospect of a future pregnancy…
 Women with previous history who wish to conceive should
be counseled and closely monitored for platelet count,
hemoglobin, LDH and peripheral smear throughout the
course of pregnancy.
 Plasma therapy should be stared at the earliest evidence of
a relapse of TTP.
 Prophylactic plasma infusion in a pregnant woman with a
history relapsing TTP may be considered.
 No association of TTP in subsequent pregnancies in
women presenting with TTP in an earlier pregnancy can be
made. Thus assurance is required foranxious women.