Thrombotic Thrombocytopenic Purpura

Presented by Dr. Nataisia Terry

Summary by Dr. Kaycie Corburn

 

The Case: 72 yo M PMH HTN and GERD presents to the ED with 1d h/o difficulty urinating and back pain. Basic labs showed thrombocytopenia. Non contrast CT showed bony sclerosis through out the vertebral bodies and splenomegaly. EKG showed new onset atrial fibrillation. The patient was admitted with intractable back pain and thrombocytopenia. At that time, the patient was noticed to also have hematuria in the foley catheter bag and bleeding of the gums. Repeat labs showed a drop in hemoglobin and platelets. In the setting of the drop in platelets and perceived active bleeding, the patient was transfused with platelets and went into acute respiratory failure. He was intubated for airway protection and transferred to the MICU. Thrombotic Thrombocytopenic Purpura (TTP) was suspected and plasmapheresis was initiated. TTP is a rare diagnosis and a hard diagnosis to make in the Emergency Room. However, prompt diagnosis can allow for the initiation of therapy and positive patient outcomes.

 

Thrombotic Thrombocytopenic Purpura (TTP)

~Epidemiology:

-Incidence is 6 cases per million per year

 

~Morbidity/Mortality:

-Untreated, the mortality is around 90%

-When treated the mortality drops to between 20-30%

 

~Pathophysiology:

-A deficiency of the ADAMTS13 metalloprotease, which is responsible for cleaving large vWF multimer

-The deficiency could be congenital or acquired (via autoantibodies)

-Large vWF multimers cause increased platelet aggregation

-Increased platelet aggregation leads to platelet clots in microvasculature leading to hemolysis and end organ damage

-Acquired TTP can be primary or idiopathic or secondary to underlying disorders such as pregnancy, HIV, malignancy, or pancreatitis

 

~Clinical findings: Only 20-30% of patients present with the pentads

–Fever

–Anemia

–Thrombocytopenia

–Renal failure

–Neurologic sequelae

 

~Key clinical features: These two features alone should warrant starting plasmapheresis

-Microangiopathic hemolytic anemia: platelet clots cause a shearing stress on RBC, which burst open and release schistocytes

-Thrombocytopenia: a consumptive process

 

~Lab Studies: Consider checking the following studies

• Complete Blood Count, Blood smear, Comprehensive Metabolic Panel, Coagulation factors, Reticulocyte count, Lactate Dehydrogenase Level, Type and Screen, Hepatitis panel, HIV assay, Haptoglobin, Troponin, Urinalysis, Urine pregnancy test

 

~Treatment options:

1. Plasmapheresis:

-First line therapy

-Plasma exchange with fresh frozen plasma

-This attempts to filter out circulating antibodies against ADAMTS13

-This works best for acquired TTP

-A response to therapy is judged based on improved mental status and improving lab measurements (LDH level, platelet count, bilirubin level, hemoglobin level, and creatinine)

2. Steroids:

-Used as an adjunct treatment

3. IVIG:

-Not first line therapy

-May be used for patients with treatment failure

4. Immunomodulator therapy:

-Examples of this include Vincristine, Cyclophosphamide, and Rituximab

-There is no current evidence that supports using these medications

5. Splenectomy:

-Only used for refractory cases of TTP

-There is a lack of evidence to support this intervention

 

~Plasmapheresis

-Uses either centrifuge mechanics or semipermeable membrane physiology to separate blood components

-The type of intravenous access required depends on the method of filtration:

-Centrifuge based filtration requires either a double lumen central line or 2 large bore antecubital peripheral intravenous lines

-Semipermeable based filtration requires higher flow rates and therefore must have a double lumen central line or hemodialysis catheter

-Red blood cells are filtered out from the plasma

-Red blood cells are returned to the patient along with donated FFP or albumin

-The antibody containing plasma from the patient is removed and discarded

 

~Plasmapharesis logistics

-Once the appropriate vascular access is in place, plasmapheresis can be initiated

-Consult Hematology at your facility for subspecialty support

-In New York State, contact the New York Blood Center at 1-866-956-NYBC (6922)

-The New York Blood Center will send equipment, supplies, and staffing to begin apheresis services

-Their services are available 24/7

-Refer to their website for more information:

http://nybloodcenter.org/medical-services/clinical-services/apheresis-services/

 

~Platelets or no platelets?

-Platelets are contraindicated

-Performing a platelet transfusion can precipitate further platelet aggregation and can lead to myocardial infarction and stroke

-CNS manifestation are the most commonly described including stroke, comma, and death

-In this case, the patient manifested as a transfusion reaction with pulmonary infiltrates and shortness of breath

-Pulmonary manifestations to platelet transfusion have not been commonly described in the literature

-Only consider platelet transfusion for life threatening bleed such as CNS bleeds; hematuria and other mucosal bleeding (such as gum bleeding) rarely lead to life threatening anemia and therefore do not justify platelet transfusions

 

~Summary: TTP is rare diagnosis and a difficult diagnosis to make in the Emergency Room, but carries a high mortality (90%) if not treated appropriately. Maintain a high index of suspicion in Emergency Room patients with a new thrombocytopenia, especially if they lack evidence of other common causes of thrombocytopenia. Pay careful attention to your clinical exam and look for evidence of altered mental status, even if subtle. A small percentage of patients have the classic pentad of signs/symptoms including fever, anemia, thrombocytopenia, renal failure, and neurologic deficits. However, in a patient with even just thrombocytopenia and hemolytic anemia, TTP should be high on the differential and suspected. In that case, avoid giving platelets unless there is a life threatening bleed such as a CNS hemorrhage. The mainstay of treatment is plasmapheresis. The medical ICU should be consulted early in most cases since these patients can be critically ill.

 

~Resources:

Disorders of Platelets and Vessel Wall Harrison’s Principles of Internal Medicine, 18e.

Aetna Clinical Policy Bulletin: ADAMTS13 Assay for Thrombotic Thrombocytopenic

Igari Atstuko et al. Monitoring ADAMTS13 Autoantibody Titer Using a Novel Quantitative Radioimmunoprecipitation Assay In Patients With Acquired Thrombotic Thrombocytopenic Purpura November 15, 2013; Blood: 122 (21).

Mannucci PM, Lavoretano S, Peyvandi S. The thrombotic microangiopathies. Blood Transf. 2005;3:120–35.

Moore JC et al. Intravenous immunoglobulin as an adjunct to plasma exchange for the treatment of chronic thrombotic thrombocytopenic purpura. Vox Sang. 2007 Aug;93(2):173-5.

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Paula Robinson et al. Evidence-Based Guidelines on the Use of Intravenous Immune Globulin for Hematologic and Neurologic Conditions Transfusion Medicine Reviews, Vol 21, No 2, Suppl 1 (April), 2007: pp S3-S8.

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Scully, Marie et al.  Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies Brit Journal of Hematology 2012.

Stieglitz, E., et al. Plasmapheresis. Medscape; Dec 2013 <http://emedicine.medscape.com/article/1895577-overview> Accessed 8/5/14.

Swisher, K., et al. Clinical Outcomes after Platelet Transfusion in Patients with Thrombotic Thrombocytopenic Purpura. Transfusion Practice, 2009; 49: 873-887.

Veyradier A., Meyer D., Thrombotic thrombocytopenic purpura and its diagnosis Journal of Thrombosis and Haemostasis, 3: 2420–2427.

Wrick-Glatzel Janice et al. Thrombotic Thrombocytopenic Purpura and ADAMTS-13: New Insights into Pathogenesis, Diagnosis, and Therapy Lab Med. 2004;35(12)

Miyata T, Kokame K, Banno F. Measurement of ADAMTS13 activity and inhibitors. Curr Opin Hematol. 2005;12:384–9.

Wun, T., et al. Thrombotic Thrombocytopenic Purpura. Medscape; June <2013http://emedicine.medscape.com/article/206598-overview> Accessed 8/5/14.