Case Challenges

Treatment options for immune thrombocytopenic purpura

A 22-year-old white man with no prior medical problems presented to the emergency department with profuse nose bleeding. He also noticed unusual mild headaches and bruises on his thighs and arms. The nose bleeding started about half an hour ago and was not responding to local pressure. He was not on any medications and denied use of illicit drugs. Physical examination revealed bleeding from the left nostril and multiple bruises on his legs, abdomen and arms. There was no evidence of pallor, lymphadenopathy or organomegaly.

His nose was packed immediately in the emergency department and stat blood specimens for complete blood count, cross and match, and chemistry were drawn. A CT scan of the head was normal. The blood tests revealed a white count of 5.0 K/uL, hemoglobin 13.0 gm/dL and platelets of 7 K/uL. His blood group was A-negative and blood chemistry was normal including creatinine, lactate dehydrogenase (LDH) and liver function tests. He was also tested negative for HIV and hepatitis. Peripheral smear showed no schistocytes, normal red blood cell morphology and many large platelets.

Wajeeha Razaq, MD
Wajeeha Razaq

A diagnosis of immune thrombocytopenic purpura was made in this otherwise healthy young man and he was started on intravenous immunoglobulin G (IVIG) at a dose of 2 gm/kg. He responded well to the treatment and his platelets increased to 45 K/uL within 24 hours. Eventually, he was discharged home at a platelet count of 80 K/uL with an appointment for follow-up in a week.

A few days later he came to the emergency department again with complaints of mild headaches and frequent nose bleeds. Blood count showed stable hemoglobin, but platelet count was 10 K/uL. The treatment with IVIG was started and steroids were added, but this time also the response was short lived. He was immunized appropriately and was referred for splenectomy. He had an excellent response and his platelet count normalized within a couple of days. Unfortunately, his disease relapsed within a month and his platelet count dropped to 15 K/uL once again.

Figure 1: Peripheral blood smear
Figure 1: Peripheral blood smear of a patient with ITP showing decreased number of platelets and a large platelet in the middle.

Source: W Razaq

How will you treat this patient further?

A) Post-splenectomy trial of steroids.
B) Vincristine infusion.
C) Rituximab weekly x 4.
D) Platelet transfusions.

Wajeeha Razaq, MD, is an Assistant Professor of Clinical Medicine in the Department of Internal Medicine, Section of Hematology/Oncology at the University of Nebraska and is a member of the HemOnc Today Editorial Board.

CASE DISCUSSION

ITP is a clinical syndrome in which a decreased number of platelets manifest as bleeding diathesis, easy bruising and capillary blood leakage into the mucus membranes and skin.

In this disease, the platelets are coated with autoantibodies to platelet membrane antigens resulting in phagocytosis by the reticuloendothelial system (figure 2). Increased destruction of platelets combined with inadequate compensation by the bone marrow results in thrombocytopenia. ITP is a diagnosis of exclusion and other cause of thrombocytopenia eg, leukemia, thrombotic thrombocytopenic purpura, drug reactions and myelodysplastic syndrome should be ruled out. Most cases of ITP especially in children are mild and self-limited and do not require any medical intervention. Some of the ITP patients have moderate to severe thrombocytopenia with clinical findings that require medical treatment.

Figure 2

The goal of the treatment is to increase the number of platelets to a safe level permitting the patients to live normal lives while awaiting spontaneous remissions. ITP is an incurable disease and relapses are common.

Asymptomatic patients with a platelet count greater than 20 K/uL should not require routine hospitalization. Although there is no specific platelet count that defines an indication of initial treatment, it has been seen in many studies that patients with platelet count between 20 K/uL to 50 K/uL rarely develop bleeding complications. For many years, glucocorticoids or IVIG remained the initial therapies of choice for these patients. Anti Rh° (D), later became available for Rh positive patients with response comparable to steroids or IVIG.

Refractory ITP is defined as persistence of ITP for more than three months, no response to splenectomy and platelet count less than 30 K/uL. There is no standard algorithm for treatment of these patients but chemotherapy agents such as azathioprine, cyclophosphamide and rituximab (Rituxan, Genentech) have been used with good response. The simplest way to treat chronic refractory ITP is to start steroids and try to achieve a safe platelet level at the lowest possible dose. Because of the adverse effects related to chronic steroid use, it can’t be given for a long time, so immunosuppressive agents have been tried with variable success rates. Rituximab, an anti-CD20 antibody, is an efficacious treatment for non Hodgkin’s Lymphoma. There has been a great interest in its use in autoimmune diseases like ITP. The mechanism of action of rituximab in ITP is assumed to be the selective depletion of CD20 B cells that affects autoantibody production. Cooper et al treated 18 chronic ITP patients with rituximab and 16 of them achieved a complete response that was maintained for 72 weeks (Br J Haematol. 2004;125:232-239). A systematic review of several uncontrolled studies demonstrated that the use of this monoclonal antibody produces response in 62% of chronic ITP patients. (Ann Intern Med. 2007;146:25–33) These studies show that rituximab has limited but valuable activity in refractory ITP patients.

We treated our patient with rituximab (375 mg/m2 weekly for four weeks) and his platelet count went up from 15 K/uL to 175K/uL within a month. He is been in remission for 18 months.

PERSPECTIVE

Perhaps a careful history of upper gastrointestinal distress would lead to endoscopy, Helicobacter pylori infection and amelioration of ITP by antibiotic treatment. Perhaps not, but worth consideration.

Harry S. Jacob, MD
HemOnc Today Chief Medical Editor

A 22-year-old white man with no prior medical problems presented to the emergency department with profuse nose bleeding. He also noticed unusual mild headaches and bruises on his thighs and arms. The nose bleeding started about half an hour ago and was not responding to local pressure. He was not on any medications and denied use of illicit drugs. Physical examination revealed bleeding from the left nostril and multiple bruises on his legs, abdomen and arms. There was no evidence of pallor, lymphadenopathy or organomegaly.

His nose was packed immediately in the emergency department and stat blood specimens for complete blood count, cross and match, and chemistry were drawn. A CT scan of the head was normal. The blood tests revealed a white count of 5.0 K/uL, hemoglobin 13.0 gm/dL and platelets of 7 K/uL. His blood group was A-negative and blood chemistry was normal including creatinine, lactate dehydrogenase (LDH) and liver function tests. He was also tested negative for HIV and hepatitis. Peripheral smear showed no schistocytes, normal red blood cell morphology and many large platelets.

Wajeeha Razaq, MD
Wajeeha Razaq

A diagnosis of immune thrombocytopenic purpura was made in this otherwise healthy young man and he was started on intravenous immunoglobulin G (IVIG) at a dose of 2 gm/kg. He responded well to the treatment and his platelets increased to 45 K/uL within 24 hours. Eventually, he was discharged home at a platelet count of 80 K/uL with an appointment for follow-up in a week.

A few days later he came to the emergency department again with complaints of mild headaches and frequent nose bleeds. Blood count showed stable hemoglobin, but platelet count was 10 K/uL. The treatment with IVIG was started and steroids were added, but this time also the response was short lived. He was immunized appropriately and was referred for splenectomy. He had an excellent response and his platelet count normalized within a couple of days. Unfortunately, his disease relapsed within a month and his platelet count dropped to 15 K/uL once again.

Figure 1: Peripheral blood smear
Figure 1: Peripheral blood smear of a patient with ITP showing decreased number of platelets and a large platelet in the middle.

Source: W Razaq

How will you treat this patient further?

A) Post-splenectomy trial of steroids.
B) Vincristine infusion.
C) Rituximab weekly x 4.
D) Platelet transfusions.

Wajeeha Razaq, MD, is an Assistant Professor of Clinical Medicine in the Department of Internal Medicine, Section of Hematology/Oncology at the University of Nebraska and is a member of the HemOnc Today Editorial Board.

CASE DISCUSSION

ITP is a clinical syndrome in which a decreased number of platelets manifest as bleeding diathesis, easy bruising and capillary blood leakage into the mucus membranes and skin.

In this disease, the platelets are coated with autoantibodies to platelet membrane antigens resulting in phagocytosis by the reticuloendothelial system (figure 2). Increased destruction of platelets combined with inadequate compensation by the bone marrow results in thrombocytopenia. ITP is a diagnosis of exclusion and other cause of thrombocytopenia eg, leukemia, thrombotic thrombocytopenic purpura, drug reactions and myelodysplastic syndrome should be ruled out. Most cases of ITP especially in children are mild and self-limited and do not require any medical intervention. Some of the ITP patients have moderate to severe thrombocytopenia with clinical findings that require medical treatment.

Figure 2

The goal of the treatment is to increase the number of platelets to a safe level permitting the patients to live normal lives while awaiting spontaneous remissions. ITP is an incurable disease and relapses are common.

Asymptomatic patients with a platelet count greater than 20 K/uL should not require routine hospitalization. Although there is no specific platelet count that defines an indication of initial treatment, it has been seen in many studies that patients with platelet count between 20 K/uL to 50 K/uL rarely develop bleeding complications. For many years, glucocorticoids or IVIG remained the initial therapies of choice for these patients. Anti Rh° (D), later became available for Rh positive patients with response comparable to steroids or IVIG.

Refractory ITP is defined as persistence of ITP for more than three months, no response to splenectomy and platelet count less than 30 K/uL. There is no standard algorithm for treatment of these patients but chemotherapy agents such as azathioprine, cyclophosphamide and rituximab (Rituxan, Genentech) have been used with good response. The simplest way to treat chronic refractory ITP is to start steroids and try to achieve a safe platelet level at the lowest possible dose. Because of the adverse effects related to chronic steroid use, it can’t be given for a long time, so immunosuppressive agents have been tried with variable success rates. Rituximab, an anti-CD20 antibody, is an efficacious treatment for non Hodgkin’s Lymphoma. There has been a great interest in its use in autoimmune diseases like ITP. The mechanism of action of rituximab in ITP is assumed to be the selective depletion of CD20 B cells that affects autoantibody production. Cooper et al treated 18 chronic ITP patients with rituximab and 16 of them achieved a complete response that was maintained for 72 weeks (Br J Haematol. 2004;125:232-239). A systematic review of several uncontrolled studies demonstrated that the use of this monoclonal antibody produces response in 62% of chronic ITP patients. (Ann Intern Med. 2007;146:25–33) These studies show that rituximab has limited but valuable activity in refractory ITP patients.

We treated our patient with rituximab (375 mg/m2 weekly for four weeks) and his platelet count went up from 15 K/uL to 175K/uL within a month. He is been in remission for 18 months.

PERSPECTIVE

Perhaps a careful history of upper gastrointestinal distress would lead to endoscopy, Helicobacter pylori infection and amelioration of ITP by antibiotic treatment. Perhaps not, but worth consideration.

Harry S. Jacob, MD
HemOnc Today Chief Medical Editor