A 1-year-old boy is brought to the emergency department for evaluation of a nosebleed that has been difficult to control. Since last week, the patient has had bouts of epistaxis that occurred with minimal trauma. His parents were previously able to control the bleeding episodes by pinching the nose and using ice, but this has not stopped the bleeding today. Temperature is 37.2 C (99 F) and pulse is 160/min. Examination shows an alert child who is well developed, anicteric, and pale. Examination of the nares shows slow, steady blood flow from the left anterior nasal septum. Cardiac examination reveals tachycardia. The abdomen is soft, nontender, and without hepatosplenomegaly. The skin has multiple ecchymoses over the left shoulder and bilateral lower extremities and many petechiae in the groin. Laboratory studies are as follows:
| Complete blood count | |
| Hemoglobin | 7.9 g/dL |
| Platelets | 22,000/mm3 |
| Leukocytes | 2,100/mm3 |
| Coagulation studies | |
| PT | 14 sec |
| Activated PTT | 34 sec |
Peripheral smear reveals morphologically normal-appearing leukocytes, erythrocytes, and platelets. Which of the following is the most likely cause of this patient's bleeding?
Aplastic anemia | |
Pathogenesis |
|
Common triggers |
|
Manifestations |
|
Diagnosis |
|
Spontaneous epistaxis, petechiae, and scattered ecchymosis often indicate an underlying coagulation disorder or platelet deficiency. Because this patient's coagulation studies (PT/PTT) are normal, a coagulation disorder is unlikely; however, the presence of pancytopenia and diminished, morphologically normal cells on peripheral blood smear strongly suggests aplastic anemia.
Aplastic anemia is a form of acquired bone marrow failure typically caused by direct toxic injury or cytotoxic T-cell destruction of multipotent hematologic stem cells. This reduces production of the precursor cells (eg, megakaryocytes) that generate all blood cell lines. Although most pediatric cases have no discernable cause (idiopathic), a minority are triggered by viruses (eg, hepatitis, parvovirus), medications, or radiation exposure.
Patients generally present with symptoms of anemia (eg, fatigue, dyspnea), thrombocytopenia (eg, bruising, bleeding, petechiae), or leukopenia (eg, infection). Examination will show no hepatosplenomegaly because significant extramedullary hematopoiesis does not occur (stem cells are damaged and cannot effectively produce cells in any organ). Laboratory results will reveal pancytopenia with impaired reticulocyte response and diminished, morphologically normal blood cells on peripheral smear. Definitive diagnosis is made with bone marrow biopsy, which usually shows profound hypocellularity and fatty infiltration.
(Choice A) Conversion of fibrinogen to fibrin is the last step in the final common pathway of the coagulation cascade. PT/PTT would be prolonged and platelet level would be normal.
(Choice B) Immune thrombocytopenia is associated with the formation of autoantibodies against platelet glycoproteins, which leads to thrombocytopenia due to platelet destruction by macrophages in the spleen. However, the other cell lines (ie, leukocytes, erythrocytes) are typically unaffected.
(Choice D) Because many coagulation factors are produced in the liver, severe liver disease (eg, cirrhosis) can cause bleeding from coagulation factor deficiency. Although thrombocytopenia can also be seen due to congestive splenomegaly, PT and PTT are generally prolonged.
(Choice E) Microvascular thrombosis can be seen with thrombotic microangiopathy. Although this can cause thrombocytopenia due to platelet consumption and anemia due to red blood cell shearing, patients would have schistocytes on peripheral blood smear.
(Choice F) Von Willebrand factor deficiency is the most common inherited coagulation disorder. Although most patients are asymptomatic, a minority have bleeding and bruising due to an impaired ability of platelets to bind to damaged endothelium. However, platelet count is normal.
Educational objective:
Aplastic anemia is a form of bone marrow failure marked by decreased production of all cell lines (ie, platelets, erythrocytes, leukocytes) and morphologically normal cells on peripheral smear. It is caused by direct toxic injury or cytotoxic T-cell destruction of multipotent hematopoietic stem cells, which reduces the precursors (eg, megakaryocytes) that generate all blood cell lines.