You are on page 1of 7

Thrombotic thrombocytopenia

ABSTRACT
INTRODUCTION
Thrombotic thrombocytopenia(TTP) is a rare disorder of coagulation dysfunction, with incidence
rate of 3/1,000,000 per year. The median age for the diagnosis of acquired TTP diagnosis is 41 years
old with a wide range from 9 to 78 years. It has a higher risk profile in the female sex and those of
African descent. It should be noted that even though TTP may be a medical condition of high
fatality, if effective and prompt medical interventions including plasma exchange and
immunosuppressant are implemented its survival rate may be increased to as high as 90%.
It classically presents as the pentad: thrombocytopenia, microangiopathic hemolytic
anemia(MAHA), neurologic symptoms, kidney failure, and fever. Thrombocytopenia is the result of
platelet deposition in microthrombi and bleeding sometimes onsets due to the interaction between
thrombocytopenia and vascular injury. MAHA is resulted from fragmentation of red blood cells
while passing through the microvasculature rich with microthrombi. Schistocytes may be a
prominent finding seen on peripheral blood smear on routine pathological investigations.
Rarely all five components of the pentad will be concurrently present in a typical patient.
Neurologic manifestations may present and can be differentiated as minor(confusion, headache) or
severe(coma, stroke, seizure) symptoms due to the underlying pathological process. It should be
noted that 40% of those patients diagnosed with TTP may develop renal insufficiency. Other
symptoms including gastrointestinal and cardiac were also seen in some cases with fever being a
lesser common symptom of presentation.
TTP was categorized into two groups: inherited and acquired. Acquired TTP is the most likely form
to have idiopathic causes of disease. It has been suggested that disease onset may be associated
with gestation, medication, infection, cancer, and autoimmune diseases.
The diagnostic testing for TTP includes: complete cell count, platelet count, peripheral blood
smear, coagulation testing(PT, aPTT, fibrinogen, d-dimer), serum chemistries and creatinine, serum
lactate dehydrogenase, serum bilirubin level, direct antiglobulin test, ADAMTS13 activity and
inhibitor testing. TTP was reported to be associated with severe ADAMTS13 deficiency, especially in
inherited type[3]. There exists the possibility that the measure of ADAMTS13 activity levels may be
utulised to provide a potential role in the diagnosis of the condition.
The treatment of TTP is relatively simple. Initiation of plasma exchange therapy rather than plasma
infusion or immunosuppressive therapy alone was suggested for better prognosis. Rituximab also
has a role in the treatment process in combination with plasma therapy and corticosteroids. It was
reported that with plasma exchange, noticeable improvements have been documented with the
various manifestations including cardiac, hematologic, neurologic and renal.
CASE REPORT
A 34-year-old Chinese man with no systemic diseases nor operation history. He was sent to
Emergency Department of YMUH-Yilan on Aug 2nd, 2015 presented with altered consciousness
while driving. He suffered from upper respiratory infection with intermittent fever and chills about
one week ago, associated with poor appetite, nausea, malaise and hematuria. In ED, brain CT
revealed no mass, intracranial hemorrhage nor extensive ischemic infarct. Intravenous
antimicrobial, antiviral agents, and sedatives were given. He was then transferred to St. Mary’s
Hospital-Luodong(SMH) for intensive care.

At SMH, his initial vital signs presented with body temperature 39.6°C, pulse rate 146/min,

respiratory rate 20/min, blood pressure 154/77mmHg. Glasgow coma scale E1V1M4 under
sedation. Pale conjunctivae and nasal bleeding were noted, associated with neck rigidity. Multiple
ecchymosis and purpura over extremities and trunk were demonstrated. His GCS progressed to
E2V1M5 after admitted to intensive care unit, with eyes deviation to left. Hemiparesis(muscle
power 2) and increased deep tendon reflex over left side accompanied.
Laboratory exams revealed a white blood cells count of 14900 cells/mm3 , a hemoglobin level of
7.6 g/dl, a platelet count of 18000 cells/mm3 . Creatinine level reported 1.3mg/dL, eGFR 67.57, AST
64IU/L. Both total and direct bilirubin demonstrated elevation: total bilirubin 2.7mg/dL, direct
bilirubin 0.6 mg/dL. Coagulation profiles were in normal ranges. Additional laboratory evaluation
including CK-MB 46.4IU/L and LDH 2512 U/L. Amphetamine, Ketamine, Morphine, and Ethyl all
reported negative.
Lumbar puncture was failed due to uncooperation and thrombocytopenia. Ceftriaxone was
initiated on Aug 2nd, and then added on Vancomycin and Acyclovir. Brain MRI on Aug 3rd revealed no
remarkable findings. No epileptiform discharge showed on electroencephalography. Lumbar
puncture was performed after PRBC and platelet transfusion, with data as followed: clear CSF; RBC
3, WBC 0; Sugar 77 mg/dl; total protein 51 mg/dl; AFB (-), Gram’s stain (-); TB PCR (-) ; Cryptococcal
Ag (-); Bacterial culture & fungal culture: no growth. Peripheral blood smear reported
normochromic RBC morphology; polychromasia 1+; Anisocytosis 1+; Microcytic 2+; normal WBC
morphology; decreased platelet. Iron profile and hemoglobin electrophoresis revealed: Fe 44 ug/dL;
TIBC 177 ug/dL; ferritin 2363 mg/mL; HbA 96.3%; HbF 1.3%.
For the followed two days, his consciousness still remained drowsy (GCS: E3V1M5). In addition, his
muscle power deteriorated with right side from 4 to 3, left side from 2 to 1. Low grade fever
persisted in spite of antimicrobial agents including Ceftriaxone, Vancomycin and Acyclovir. On Aug
5th midnight, newly onset convulsion with jerky rigorous involuntary movement of upper extremities
happened once. The second episode happened at 6AM. Worsened consciousness (GCS E1V1M2)
and muscle power (right side 2, left side 1) were noted. Fever flare up to 39.5’C occurred on Aug 5th.
Laboratory analysis on Aug 5th demonstrated: hemoglobin level of 5.9 g/dl, a platelet count of 8000
cells/mm3 . Stool occult blood reported 2+. Mild brain swelling with no evidence of delayed
intracranial hemorrhage or infarct was seen on brain CT. At 2PM, 3rd seizure attacked. Plasma
exchange and high dose steroid with methylprednisolone were initiated.
NSTEMI occurred on Aug 10th morning. Conservative treatment was carried out due to high risk of
bleeding tendency. Rituximab was prescribed during Aug 10th to Aug 11th. His mental status
improved gradually, becoming able to answer name, age and time. Followed platelet and LDH level
returned to normal range. Antimicrobial agents were stopped on Aug 12th, and intravenous
methylprednisolone was gradually tapered. He was transferred to ordinary ward on Aug 18th.
Plasma exchange was discontinued on Aug 23th since his consciousness, memory and calculation
functions improved. Intravenous methylprednisolone was replaced by oral from. He was discharged
on Aug 26th.
DISCUSSION
TTP is known as a fatal disease with high mortality rate of about 90% without proper treatment.
Due to the damage caused by platelet microthrombi in small vessels, there are potential risks to
vital organ such as kidney, heart and brain. This case shows the importance of awareness and early
management in case diagnosed with TTP.
A presumptive diagnosis of TTP must be made while MAHA and thrombocytopenia are
demonstrated, followed by the immediate initiation of therapy. It is suggested that patients with
presumptive diagnosis of TTP should be immediately treated with plasma exchange. Delayed
therapy may lead to serious consequences. Diagnosis without full classic pentad is necessary since
all features are rarely seen at the same time.
The integration of MAHA, thrombocytopenia, markedly elevated LDH, elevated bilirubin, and
negative Coombs testing indicate for confirmed diagnosis. On the other hand, severe deficiency of
ADAMTS13 with an inhibitor provides further evidence. It is essential to detect clinical presentations
of TTP as soon as possible. Early detection and intervention including plasma exchange is proved to
raise the survival rate of TTP. In addition, complications of vital organs should be under surveillance
with active managements.
Being specifically to cardiac complications, it has been reported that Thrombotic thrombocytopenic
Purpura (TTP) is associated with arrhythmia, cardiogenic shock, myocardial infarction, heart failure ,
and even sudden cardiac death. Those complications are probably related to the injury of cardiac
tissue leaded by diffuse thrombi. In previous study, it was estimated that 5.7% of patients with TTP
has acute myocardial infarction. Upon all cardiac complications, acute MI is found to be the most
common one in patients with TTP.
In our case, plasma exchange was initiated at the 3rd day of admission, while myocardial infarction
was detected at 8th day. Our case was well-being before and had no predictors of AMI. The
correlation and etiology between TTP and MI remain unclear. However, there is study about
predictors of AMI in patient with TTP. Predictors were statistically showed to be older age, acute
renal failure, congestive heart failure, and history of coronary artery disease. It was also reported
that monitor of Troponin level might help to warn myocardial damage early. In previous study, it
was suggested that routine evaluation including cardiac enzyme and EKG should be checked for
warranty.
In summary, we have a case of TTP presented with neurological deficit, MAHA, thrombocytopenia
and fever. He has good response to plasma therapy, whereas NSTEMI was seen once during
hospitalization. No subsequent damage to cardiac system was detected, and he recovered well
under plasma exchange and corticosteroid. Our case illustrates that the awareness of clinical
symptoms as well as good collaboration with laboratory analysis are essential for early diagnosis.
Routine survey with cardiac enzymes and EKG should be applied to all patients with TTP, even
without predictors for AMI. Furthermore, studies with appropriate intervention of AMI in TTP are
required for follow-up treatment.
REFERENCES
[1] Takimoto T, Nakao M, Nakajo T, Chinen Y, Kuroda J, Taniwaki M. Acute myocardial infarction as
the initial thrombotic event of thrombotic thrombocytopenic purpura. Blood Coagulation &
Fibrinolysis. 2016;27(8):948-951.
[2] Veyradier A, Obert B, Houllier A, Meyer D, Girma JP. Specific von Willebrand factor-cleaving
protease in thrombotic microangiopathies: a study of 111 cases. Blood. 2001; 98:1765–1772
[3] Pier M M, Flora P. TTP and ADAMTS13: When Is Testing Appropriate? ASH Education
Book.January 1, 2007 vol. 2007 no. 1 121-126
[4] Mouabbi J, Zein R, Kafri Z, Al-Katib A, Hadid T. Thrombotic thrombocytopenic purpura presenting
as acute coronary syndrome. Clinical Case Reports. 2016;4(8):736-739.
[5]Balasubramaniyam N, Kolte D, Palaniswamy C, Yalamanchili K, Aronow W, McClung J et al.
Predictors of In-hospital Mortality and Acute Myocardial Infarction in Thrombotic
Thrombocytopenic Purpura. The American Journal of Medicine. 2013;126(11):1016.e1-1016.e7.
[6] Dhawan S, Tak T. Myocardial infarction in a patient with thrombotic thrombocytopenic purpura.
International Journal of Cardiology. 2004;95(2-3):339-341.
[7] Wajima T, Johnson E. Sudden Cardiac Death From Thrombotic Thrombocytopenic Purpura.
Clinical and Applied Thrombosis/Hemostasis. 2000;6(2):108-110.
[8] Patschan D, Witzke O, Dührsen U, Erbel R, Philipp T, Herget-Rosenthal S. Acute myocardial
infarction in thrombotic microangiopathies--clinical characteristics, risk factors and outcome.
Nephrology Dialysis Transplantation. 2006;21(6):1549-1554.
[9] Wahla A, Ruiz J, Noureddine N, Upadhya B, Sane D, Owen J. Myocardial infarction in thrombotic
thrombocytopenic purpura: a single-center experience and literature review. European Journal of
Haematology. 2008;81(4):311-316.
[10] Ranjan P, Madan R A, Smith G, Paras K, and Anthony A D. Cardiac Complications in Thrombotic
Thrombocytopenic Purpura: Data from Nationwide Inpatient Sample. Blood. 2014 124:2793;

[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]