Platelet disorders and their implications on physical therapy intervention

Rehabilitation Oncology,  2001  by Zavadsky, Aaron Joseph

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INTRODUCTION

Today, oncology patients are subjected to a myriad of treatments to both prolong and save lives. Some of these procedures include bone marrow transplants, chemotherapy, and radiation. Unfortunately, potentially serious side effects may arise from these procedures. One such life-threatening complication is a decrease in the number of platelets (thrombocytopenia). Platelets are cells in whole blood that help the blood to clot. If one's platelet levels are low, he/she faces the risk of abnormal bleeding. This bleeding may occur for 2 main reasons: (1) the patient's bone marrow cannot produce enough platelets, or (2) their platelets have been destroyed by disease.1

To better understand this complication, this paper will explore platelet structure and function. In addition, the paper will investigate the disorders linked to both abnormal platelet destruction and production and potential treatments. Finally, this paper will discuss the implications these disorders have on physical therapy intervention.

PLATELETS

As with erythrocytes and leucocytes, platelets are produced in the bone marrow. They originate as anucleate fragments of megakaryocyte cytoplasm, a giant cell in the bone marrow.2 Once mature, the platelet has a complex phospholipid membrane. This membrane contains several integral membrane proteins that serve as receptors for plasma proteins. These proteins assist in platelet adhesion and aggregation.3 In addition, platelet dense bodies and secretory granules within the platelet act as a storage pool. This pool contains substances, such as ADP (adenosine diphosphate), that also favor aggregation.

Once a platelet is released from the bone marrow, it circulates for approximately 8-10 days. Normal platelet levels in the blood are between 150,000-400,000/microliter. This count reflects the balance between production and destruction.2 In patients battling cancer, either the disease or its treatments may drastically disrupt this balance. As a result, patients may develop dangerous thrombocytopenia.

As platelet levels drop, the risk for serious complications rises. At 100,000/microliter, normal clotting is still possible. Patients need at least 50,000/microliter for surgeons to perform procedures. Patients with platelet counts of 30,000-50,000/microliter have bruising after negligible trauma. Those with counts of 10,000-30,000/ microliter experience spontaneous bruising, menorrhagia, and prolonged bleeding with injury. Finally, those with counts of less than 10,000/microliter have mucosal bleeding (epistaxis, gastrointestinal, and genitourinary) and are at risk for CNS bleeding.4

When a blood vessel is injured, subendothelial tissue is exposed and platelets adhere to it. This adherence, along with the generation of thrombin due to plasma coagulation, stimulates the release of arachidonic acid from the phospholipid membrane. Arachidonic acid is converted to TxA^sub 2^ and thrombin stimulate the release of granules and dense bodies and ADP The high local concentration of thrombin, TxA ^sub 2^ and ADP induces changes in the platelet membrane that provide for the assembly of clotting factors such as fibrinogen.4 Finally, fibrinogen forms a bond between adjacent platelets, creating a hemostatic plug that prevents further bleeding.2

DISORDERS OF INCREASED PLATELET DESTRUCTION

Immune Thrombocytopenia Purpura (ITP)

Immune thrombocytopenia purpura (ITP) is one of the most common causes of thrombocytopenia encountered in medicine. The disorder is estimated to affect approximately 1 in 10,000 in the general population and account for 0.18% of hospital admissions.' In respect to cancer, ITP is more frequently associated with lymphoproliferative diseases and less frequently with Hodgkin's Disease (HD).5 ITP induces accelerated platelet destruction without abnormalities in leukocyte and erythrocyte levels. This destruction is caused by an immune system abnormality that leads to the development of autoantibodies that bind to the platelet-membrane antigens and shortens its life span.5 This destruction most often occurs in the spleen.

One potential cause of ITP is related to Graft vs. Host Disease (GVHD) following an allogenic bone marrow transplant (marrow from another person). Persistent autoimmune thrombocytopenia after an allogenic BMT is often associated with poor patient prognosis. ITP presents an additional complication to the clinical course of BMT patients with GVHD. A study conducted by Anasetti et al, found that the presence of platelet-bound autoantibodies and the occurrence of GVHD were associated with lower platelet counts and shorter platelet survival.7

ITP is rarely observed in HD. ITP occurs in less than 1% of patients with HD.3 A retrospective study conducted by Xiros et al5 looked at 492 patients with HD. Based on the exclusion criteria, only 5 patients exhibited platelet-bound autoantibodies with abundant megakaryocytes in the bone marrow.

In response to this abnormal destruction of platelets, 2 principal treatments attempt to reverse the condition. The initial treatment option is through corticosteroids (prednisone). Corticosteroids alter the body's immune system to prevent it from attacking platelets.8 The goal of steroids are to reverse and prevent severe ITP for a sufficient period to promote spontaneous remission.3 In the study by Xiros et al, they stated that 15% to 50% of patients with ITP achieved a complete remission with the use of steroids.5 The mechanism of action is unknown. However, evidence suggests that one reason is by inhibiting antibody production.9