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58. Thrombotic Thrombocytopenia Purpura (TTP): “Who Are You Calling a FAT RN?”
Keywords
TTPThrombotic thrombocytopenia purpuraMicroangiopathic hemolytic anemiaThrombocytopeniaPlasmapheresisThrombotic microangiopathyCase
Shortness of Breath and Irregular Heartbeat.
Pertinent History
The patient is a 48-year-old female with complex history including heart failure with reduced ejection fraction, chronic relapsing thrombotic thrombocytopenia purpura (TTP), paroxysmal atrial fibrillation, chronic obstruction pulmonary disease (COPD), and hyperthyroidism who presents for evaluation of shortness of breath. The patient had these symptoms for approximately 2 days. She has also noticed some bruising on her arms and legs and has felt fatigued. She stated this is what her previous TTP relapses have felt like. She denied any chest pain or cough. She endorsed subjective fevers without measured temperatures. She had no lower extremity swelling. Reportedly, she called EMS, and when they hooked her up to the monitor, they were concerned for atrial fibrillation with rapid ventricular response, and she was given 20 mg of Cardizem prior to arrival. She said this did not help.
Pertinent Physical Exam
Except as noted below, the findings of the complete physical exam are within normal limits.
Blood pressure 119/77, pulse 117, temperature 97.8 °F (36.6 °C), temperature source Oral, respiratory rate 26, SpO2 95.00%.
Constitutional: She is oriented to person, place, and time. She appears well-developed and well-nourished. She appears in distress.
Cardiovascular: Increased rate, regular rhythm, normal heart sounds, and intact distal pulses. No murmur heard.
Pulmonary/chest: Breath sounds normal. She is in respiratory distress. She has no wheezes. She has no rales. Dyspnea and tachypnea are present. She is unable to speak in full sentences.
Abdominal: Soft. She exhibits no distension. There is no tenderness.
Neurological: She is alert and oriented to person, place, and time. She exhibits normal muscle tone. Coordination normal. Exam changes during the course of the ED stay.
Skin: Skin is warm and dry. Petechiae noted. She is not diaphoretic. There is pallor and mild jaundice present. Ecchymosis to left arm under BP cuff and bilateral ankles.
PMH
Heart failure with reduced ejection fraction (EF = 15%)
Previous thrombotic thrombocytopenic purpura with relapse several years prior
Paroxysmal atrial fibrillation
Pertinent Test Results
Test | Result | Units | Normal range |
|---|---|---|---|
WBC | 16.4 | K/uL | 3.8–11.0 103/mm3 |
Hgb | 12.3 | g/dL | (Male) 14–18 g/dL (Female) 11–16 g/dL |
Platelets | 41 | K/uL | 140–450 K/uL |
BUN | 33 | mg/dL | 6–23 mg/dL |
Creatinine | 1.48 | mg/dL | 0.6–1.5 mg/dL |
Glucose | 231 ↑ | mg/dL | 65–99 mg/dL |
Troponin | 24.89 | ng/ml | <0.04 ng/dl |
BNP | 2283 | pg/ml | <100 pg/ml |
Total bili | 2.8 | mg/dL | 0.2–1.4 mg/dL |
ED Management
On arrival, she was significantly tachycardic but otherwise hemodynamically stable. Her respiratory effort was increased, with her unable to speak complete sentences, but her oxygenation was within normal limits on a nasal cannula. We had initial concerns for repeat TTP exacerbation with a differential diagnosis including CHF exacerbation, acute coronary syndrome, or pulmonary pathology such as pneumonia or pneumothorax.
Initial chest X-ray showed cardiomegaly and a pleural effusion consistent with volume overload in the setting of CHF with poor ejection fraction. Chemistry revealed an acute kidney injury with a creatinine of 1.48. Hemoglobin was normal at 12. Platelets returned with thrombocytopenia at 41, with most recent previous values of 150–170. The clinical picture was consistent with an acute TTP. This was confirmed over the phone with the lab as they reported schistocytes on her smear. To complicate matters, her troponin came back significantly elevated at 24, consistent with cardiac ischemia. BNP was also elevated above 2000. At this point, there was concern that TTP was causing acute platelet plugging and an acute myocardial infarction; however serial EKGs did not show ST elevation.
We consulted hematology, who recommended plasmapheresis after bedside evaluation of the patient. The patient also had runs of ventricular tachycardia and continued to be tachycardic and symptomatic. Cardiology was consulted and recommended an amiodarone bolus followed by a drip.
Updates on ED Course
During the patient’s ED course, she became hypoxic with oxygen saturations in the low 80s on nonrebreather and had declining mental status, with subsequent intubation in the ED. An apheresis catheter was placed, and the procedure was complicated by the lateral port clotting at the time of line placement. Per recommendations of hematology, the line was unclogged using tissue plasminogen activator (tPA). Hematology also recommended corticosteroids, which were administered. The patient also became secondarily hypotensive after intubation and remained hypotensive in the 80s over 50s throughout the rest of her ED stay. She was treated with multiple liters of IV fluids after intubation, with admission to the medical intensive care unit in critical condition.
Learning Points
Priming Questions
- 1.
What signs and symptoms should prompt consideration of and evaluation for TTP, and what are the most reliable clinical indicators of its presence?
- 2.
How can TTP be distinguished from other forms of microangiopathic hemolytic anemia, and what differential diagnoses can present with similar symptoms?
- 3.
What are the critical actions that can be performed in the emergency department to increase the chance of patients with TTP surviving their disease?
Introduction/Background
- 1.
TTP is a form of microangiopathic hemolytic anemia (MAHA) [1] , and like other forms of MAHA such as hemolytic uremic syndrome (HUS) or disseminated intravascular coagulation (DIC), it is characterized by the destruction of erythrocytes associated with thrombosis in the small blood vessels of multiple organs.
- 2.
TTP is a rare disorder, with an annual incidence of between 2 and 4 patients per million per year [1, 2]. Mortality for TTP was originally over 90%, but contemporary advances in care have decreased the mortality to as low as 10% with conventional treatments [1].
There is demographic variation in the incidence of TTP, with women and patients of African descent experiencing disproportionately higher rates of the disease [2, 3]. Large cohorts have demonstrated women making up over 70% of cases of idiopathic TTP and patients of African descent making up over a quarter of the patient population.
The majority of cases are idiopathic, but precursors associated with the development of TTP include preceding infections, HIV, pregnancy, autoimmune diseases (such as systemic lupus erythematosus), malignancy, and certain medications (e.g., quinine, ticlopidine, and clopidogrel) [1, 4].
- 3.
Patients with idiopathic TTP have a 40% risk of recurrence, which usually manifests as a single episode within the first year after initial diagnosis, and may have a less severe presentation [5].
Pathophysiology
- 1.
In normal physiology, a metalloproteinase referred to as ADAMTS13 circulates at functional levels in the bloodstream. As shear stress on the endothelial cells of the blood vessel walls exposes von Willebrand factor (vWF) multimers, ADAMTS13 cleaves these multimers inactivating their pro-thrombotic effect [6].
For the nerds, ADAMTS13 is “a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13.”
Normal Function of vonWillebrand’s Factor
Courtesy of Colin Kaide, MD (Published with kind permission of © Colin G. Kaide 2019. All Rights Reserved
- 2.
Patients with TTP have a deficiency of ADAMTS13, either due to a genetic defect leading to decreased production or an inhibiting antibody deactivating the enzyme [6, 7]. vWF thereby accumulate, promoting platelet adhesion and the deposition of microthrombi platelets in small blood vessels, with resulting organ damage. Because platelet activation typically does not happen in this process, the clotting cascade likewise remains mostly unactivated leading to very little fibrin in these predominantly platelet-vWF plugs. Consumption of platelets accounts for the notable thrombocytopenia (<50 × 109/L, often as low as 10–15 × 109/L).
Those born with a hereditary ADAMTS13 deficiency have homozygous or double-heterozygous autosomal recessive mutation of the ADAMTS13 gene and manifest with symptoms in childhood [6]. These patients are treated with scheduled plasma transfusions to supplement levels of ADAMTS13.
Patients with acquired TTP have both deficiency levels of ADAMTS13 and a detectable inhibiting antibody causing autoimmune destruction of the functional enzyme [6].
vWF Multimers and Antibodies to ADAMTS13
Courtesy of Colin Kaide, MD. (Published with kind permission of © Colin G. Kaide 2019. All Rights Reserved)
Virtually any organ system can be affected by ischemic damage caused by the microthrombi (e.g., central nervous system involvement with neurologic deficits, acute kidney injury, myocardial infarction) [1]. Notably, pulmonary compromise secondary to microthrombi without another identifiable cause is rare, possible due to lower shear stress in the pulmonary vasculature or the high compliance and collateral circulation of pulmonary vessels [8].
Micro Angiopathic Hemolytic Anemia—MAHA
Courtesy of Colin Kaide, MD. (Published with kind permission of © Colin G. Kaide 2019. All Rights Reserved)
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