A 32-year-old woman complains of bleeding gums while brushing her teeth and easy bruising of several weeks’ duration. She has no significant past medical history, has had no previous surgery, and does not take any medication. She denies consumption of alcohol, tobacco, or illicit drugs. On examination, you notice several petechiae on her legs and bruises over the knees. The results from her head and neck, cardiopulmonary, and abdominal examinations are unremarkable. No masses are palpable in the abdomen. The laboratory evaluation reveals a normal white blood cell count and normal hemoglobin and hematocrit values. Results from serum chemistry studies are within the normal range. Her platelet count is 27,000/mm3. A bone marrow biopsy is performed, demonstrating the presence of numerous megakaryocytes but no evidence of malignancy.
What is the most likely diagnosis?
What is the mechanism associated with this disease process?
What is your next step in treatment?
ANSWERS TO CASE 49: Immune Thrombocytopenia Purpura (Splenic Disease)
Summary: A 32-year-old woman presents with easy bruisability, gum bleeding and petechiae, and thrombocytopenia. The bone marrow aspirate shows an increased number of megakaryocytes (normal functions).
• Diagnosis: Immune thrombocytopenia purpura (ITP).
• Mechanism responsible for the process: ITP is associated with the production of antiplatelet immunoglobulin G (IgG) by the spleen.
• Next step: The initial treatment is with corticosteroids. Seventy-five percent of patients respond to corticosteroids, but the best long-term results are achieved with splenectomy.
ANALYSIS
Objectives
1. Become familiar with the role of splenectomy in the treatment of ITP.
2. Be familiar with splenic function and the complications associated with the loss of splenic function.
3. Be familiar with indications for splenectomy other than traumatic injuries.
Considerations
This patient exhibits many of the common clinical manifestations of thrombocytopenia, which include ecchymoses, gum bleeding, purpura, excessive vaginal bleeding, and gastrointestinal tract bleeding. Mechanisms producing thrombocytopenia include inadequate production because of primary or secondary bone marrow dysfunction, splenic sequestration (hypersplenism), and increased platelet destruction. ITP is an acquired disorder leading to increased platelet destruction because of the production of antiplatelet IgG by the spleen. The spleen may further contribute to thrombocytopenia by functioning as a primary site of sequestration and destruction of sensitized platelets. ITP is two to three times more common in women than men. The diagnosis of ITP is one of exclusion, which requires a careful search for possible precipitating factors such as medications and infections. The diagnosis requires demonstration of a normal to hypercellular megakaryocyte count in the bone marrow, indicating a response to the increased peripheral destruction. Splenomegaly is rare in ITP, and its presence should suggest another source of thrombocytopenia, such as hemolytic disease.
APPROACH TO: Immune Thrombocytopenia Purpura
The spleen has a number of important functions, including a significant although not indispensable role in host cellular- and humoral-mediated immunity and phagocytic activities. It removes old erythrocytes (120 days old) and platelets (10-14 days old). It also removes abnormal intracellular erythrocyte particles (Howell-Jolly bodies, Heinz bodies, and Pappenheimer bodies) and erythrocytes with abnormal membranes. The spleen is also a site of opsonins (tuftsin and properdin) and antibodies (particularly IgM) production.
CLINICAL APPROACH
A carefully recorded history and a physical examination are important in the diagnosis of ITP. A bone marrow aspirate is also necessary to confirm the diagnosis. The management of ITP varies according to the severity of the thrombocytopenia, where patients with asymptomatic platelet counts above 50,000 may simply require monitoring, and some asymptomatic patients with platelet counts of 30,000 to 50,000 may also be monitored. The initial treatment for symptomatic patients or those with lower platelet count is corticosteroids, which leads to an increased platelet count in 50% to 75% of patients. Other medical therapies include administration of intravenous immunoglobulins, plasmapheresis, and chemotherapeutic agents.
Splenectomy
Splenectomy is recommended for patients who do not respond to steroids, those who require an excessively high-steroid dose, and those who require chronic steroid therapy (>1 year). The platelet count can be expected to rise shortly after splenectomy, and sustained remissions are seen in more than 80% of cases. The best indication that splenectomy will be of lasting benefit is an increase in the platelet count with corticosteroid therapy. Patients who are refractory to corticosteroid treatment have a lower rate of long-term remission (approximately 60%). Spontaneous remission occurs in most children (85%), and splenectomy is rarely indicated. When splenectomy is needed, it should be delayed until after 4 years of age, at which time the risk of postsplenectomy sepsis is dramatically reduced. Laparoscopic splenectomy has been shown to be safe and effective. Furthermore, patients undergoing laparoscopic splenectomy tolerate feeding sooner, require less pain medication, and are discharged from the hospital sooner than those undergoing open splenectomy. Platelet transfusions generally are not required despite low platelet counts unless bleeding is uncontrollable. Platelet transfusion should be withheld intraoperatively until just after the spleen is removed; if given before this time, they are consumed and confer minimal benefit. A systemic review of articles published between 1996 and 2004 reported complete response of 66% and partial response of 88% following splenectomy for ITP.
Splenectomy Other Than for ITP
Traumatic injury has been the most common indication for splenectomy. Other common nontraumatic indications for splenectomy may be categorized as red cell–, white cell–, and platelet-related disorders, and these include congenital hemolytic anemias, such as hereditary spherocytosis and thalassemia major. Myeloproliferative disorders may lead to massive splenomegaly, which can cause symptoms that are best relieved by splenectomy. Splenectomy for myeloproliferative disorders is performed primarily for symptomatic relief.
Because of the loss of splenic immunologic function following splenectomy, postoperative infectious complications may occur, such as wound infections and intra-abdominal abscesses. Overwhelming postsplenectomy sepsis (OPSS) is an uncommon but well-recognized potential complication associated with splenectomy. The risk of OPSS depends on the age of the patient and the reason for splenectomy. It occurs in 0.3% of adults and 0.6% of children and is more common when splenectomy is performed for hematologic disease compared to splenectomy for trauma. OPSS most commonly develops within the first 2 years after splenectomy, although it can occur later. The typical onset of this clinical syndrome is often insidious and marked by nonspecific symptoms of malaise, headache, nausea, and confusion; it can progress rapidly to shock and death. Early medical evaluation at the first signs of illness is important in decreasing mortality. The mortality of OPSS exceeds 50% in children and is approximately 20% in adults. The most common organisms are encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae B, and Neisseria meningitidis, which are typically killed by the immunologic functions of the spleen. All patients undergoing planned elective splenectomy should receive a polyvalent pneumococcal vaccination 2 weeks before surgery. Children and all immunosuppressed patients should be vaccinated against pneumococcus, H influenzae B, and meningococcus.
COMPREHENSION QUESTIONS
49.1 A 44-year-old woman has recurrent thrombocytopenia following a 4-week course of corticosteroid therapy for ITP. Her platelet count has decreased from the initial posttreatment level of 120,000 to 75,000. The patient has remained asymptomatic without further treatment for the past 3 months. Which of the following is the most appropriate recommendation for this patient at this time?
A. Laparoscopic splenectomy because she has had a favorable but unsustainable response to steroids treatment
B. Intravenous immunoglobulins
C. Observation
D. Vaccination against pneumococcus, H influenzae B, and meningococcus, followed by laparoscopic splenectomy 2 weeks later
E. Plasmapheresis
49.2 A 20-year-old man sustained blunt trauma to the spleen when his car crashed into a tree. During his exploratory laparotomy, splenic lacerations were identified and treated with a partial splenectomy. Based on report, approximately one-third of the splenic mass was preserved. Which of the following studies may be helpful to determine if the patient has retained splenic functions following this procedure?
A. A CT scan of the abdomen
B. An MRI
C. A peripheral blood smear
D. Purified protein derivative (PPD) skin test
E. C-reactive protein level
49.3 In which of the following individuals is fever most likely overwhelming post-splenectomy sepsis syndrome (OPSS)?
A. A 30-year-old man who underwent splenectomy for trauma 3 years ago
B. An 8-year-old boy who underwent splenectomy for complications related to acute lymphocytic leukemia 2 years prior
C. A 60-year-old man with hypercoagulable state and splenic vein thrombosis and partial splenic infarct
D. A 12-year-old boy with history of trauma and partial splenectomy at the age of 8
E. A 32-year-old pregnant woman who underwent splenectomy for ITP during the second trimester of pregnancy
49.4 In which of the following patients is splenectomy for ITP most likely to provide long-term remission?
A. Patients with an enlarged spleen
B. Patients with a high reticulocyte count
C. Patients younger than 4 years
D. Patients who respond to corticosteroid therapy
E. Patients with petechiae
ANSWERS
49.1 C. Observation is reasonable in this patient with ITP, initial response to corticosteroids, and current level of thrombocytopenia. Further medical or surgical treatment may be appropriate if the patient’s platelet counts drop below the 30,000 to 50,000 range, or if the patient develops bleeding or bleeding complications.
49.2 C. A peripheral blood smear may demonstrate Howell-Jolly bodies, Heinz bodies, and Pappenheimer bodies if the patient’s spleen is unable to scavenge old and abnormal RBCs. The presence of these peripheral smear abnormalities indicates that the absence of normal immunological functions of the spleen is not clear.
49.3 B. OPSS is a rare condition, but pretest probability suggests that this condition occurs more commonly in children in comparison to adults, and the condition is more likely to occur following splenectomy for primary hematological disorders.
49.4 D. The patient group that has the best response to splenectomy consists of patients with ITP who respond to corticosteroid therapy. High reticulocyte count only indicates functioning bone marrow and does not predict outcome associated with splenectomy for ITP. Enlarged spleen is not a common finding associated with ITP, therefore would most likely not lead to resolution of thrombocytopenia following splenectomy. ITP in children is frequently self-limiting; therefore splenectomy is rarely indicated.
CLINICAL PEARLS
Splenomegaly is rare in ITP.
Splenectomy for ITP is most likely to provide long-term remission in patients who respond to corticosteroid therapy.
OPSS is an uncommon but well-recognized potential complication associated with splenectomy; it has a higher incidence in children than in adults.
Bone marrow aspirates from ITP patients typically reveal normal or increased number of megakaryocytes, thus indicating normal bone marrow response to low circulating platelet counts.
REFERENCES
Beauchamp RD, Holzman MD, Fabian TC, Weinberg JA. The spleen. In: Townsend CM Jr, Beauchamp RD, Evers BM, Mattox KL, eds. Sabiston Textbook of Surgery. 18th ed. Philadelphia, PA: Saunders Elsevier; 2008:1624-1652.
Kojouri K, Vesely SK, Terrelll DR, et al. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systemic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood. 2004;104:2623-2634.
Park AE, Godinez CD. Spleen. In: Brunicardi FC, Andersen DK, Billiar TR, et al, eds. Schwartz’s Principles of Surgery. 9th ed. New York, NY: McGraw-Hill; 2010:1245-1265.
Taghizadeh M, Muscarella II P. Splenectomy for hematologic disorders. In Cameron JL, Cameron AM, eds. Current Surgical Therapy. 10th ed. Philadelphia, PA: Elsevier Saunders; 2011:473-479.