Week 39: Oncology and Bleeding

The patient has thrombotic thrombocytopenic purpura (TTP). The classic pentad of TTP includes CNS abnormalities, renal pathology, fever, microangiopathic hemolytic anemia, and thrombocytopenia. However, diagnostic criteria have recently been simplified to include all adults with microangiopathic or microvascular hemolytic anemia and thrombocytopenia with no other explanation for these findings. TTP shares many clinical and laboratory features of HELLP syndrome. HELLP syndrome is less common before 24 weeks gestation. The derangements in hemoglobin and platelet levels are more severe in TTP. The mainstay of treatment for TTP is plasmapheresis (plasma exchange), which can achieve remission of disease in 80% of patients. If plasmapheresis cannot be immediately performed, fresh frozen plasma (FFP) should be administered until apheresis can be performed.

DDAVP stimulates the release of VWF, Factor VIII, and tissue factor. It may be used in bleeding episodes with mild Hemophilia A and von Willebrand disease. It does not affect Factor IX and so would not help in Hemophilia B. DDAVP does have beneficial effects on platelet function but would not help in the setting of thrombocytopenia.

D-dimer has an NPV of 99% in the diagnosis of DIC. If this test is negative, the clinician can be nearly certain the patient does not have DIC.

This patient most likely has tumor lysis syndrome, characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia. The tetany (chvostek’s sign of tapping on facial nerve causing muscle twitching) and hyper-reflexia are likely secondary to the hypocalcemia. A uric acid level is the most important test to aid in this diagnosis. Treatment is generally supportive with fluids and correction of electrolyte abnormalities. While hypoparathyroidism can cause low calcium, it will not cause the renal insufficiency seen in tumor lysis syndrome. Neither a CBC nor a peripheral smear are likely to aid in this diagnosis.

The patient in this question has hemolytic uremic syndrome, of which the acute renal failure is the leading cause of morbidity and mortality. If anuric, these patients require plasma exchange therapy, dialysis, and/or monoclonal antibody treatment.

This patient is most likely suffering from leukostasis secondary to blast crisis. The most important treatment in this case is immediate induction chemotherapy. If induction chemotherapy is unavailable, leukaphoresis and hydroxyurea may be used as temporizing measures but the definitive treatment is induction chemotherapy. IV rasburicase is the treatment for severe tumor lysis syndrome.

This patient most likely has AML, which can present with the above gingival findings due to infiltration by tumor cells. Of note, the CBC can vary in patients with AML. Normocytic anemia and thrombocytopenia are common, however the white blood cell count may be low, normal, or elevated. Lymphadenopathy is rare in AML, in contrast to ALL in which it is a common presenting symptom. Definitive diagnosis of AML is by bone marrow biopsy.

Hypercalcemia is generally a product of another underlying disorder and not a primary process in itself. Causes are grouped into four categories: malignancy (primary hematologic, metastases to the bone, or parathyroid producing tumor), hyperparathyroidism, increased intake (milk-alkali syndrome, vitamin D or A toxicity), and increased bone breakdown (immobilization, Paget disease). Clinically, patients experience lethargy, weakness, myalgias, constipation, and anorexia. The clinical presentation is often remembered by the mnemonic “bones, stones, groans and psychiatric overtones.” The first step in treatment is aggressive hydration. The addition of intravenous bisphosphonates (e.g. zoledronic acid) inhibits calcium release from bone. It is usually reserved for hypercalcemia associated with malignancy.

Plasma exchange is the treatment for patients presenting with thrombotic thrombocytopenic purpura (TTP). Patients with this diagnosis have high mortality and should be treated as soon as possible. In a patient with altered mental status, severe thrombocytopenia, and neurologic symptoms, thrombotic thrombocytopenic purpura should be suspected. Patients commonly present with weakness, gastrointestinal symptoms, or neurologic symptoms. Neurologic manifestations may include transient neurologic deficits, confusion, coma, and headache. The classic presentation of fever, renal failure, anemia, thrombocytopenia, and severe neurologic symptoms only occurs in a small percentage of patients. The pathophysiology of TTP involves abnormal platelet aggregation secondary to an abnormality in ADAMTS13, which leads to microangiopathic hemolytic anemia, characterized by schistocytes on blood smear, thrombocytopenia, and end-organ damage.

IV immunoglobulin (A) is the treatment for patients presenting with immune thrombocytopenia (ITP). Patients with ITP will have thrombocytopenia without any clear etiology and therefore should be a diagnosis of exclusion. Patients with ITP will not have evidence of microangiopathic hemolytic anemia or signs of end-organ damage. A lumbar puncture (B) is indicated in a patient suspected to have a CNS infection. In a patient with a normal white blood cell count and no fever, a CNS infection is less likely. Also, the chances of an epidural hematoma would be higher in a patient who has a platelet count of 15 x 109/L. The risks of a lumbar puncture outweigh the benefits in a patient with severe thrombocytopenia and low clinical suspicion for infection. A platelet transfusion (D) is unnecessary in a patient with significant thrombocytopenia unless there is evidence of active bleeding or a procedure is indicated and there is a risk of significant bleeding during the intervention. There is also a potential risk with platelet administration in patients with TTP, since platelet aggregation may worsen as the result of transfusion.

Severe neutropenia is defined as having an absolute neutrophil count less than 500 cells/microL which increases the risk of spontaneous serious bacterial infection. Neutropenia can be inherited or more usually acquired while on chemotherapy. Viral infections can cause transient neutropenia and if discovered incidentally further workup may be indicated. Patients with known severe neutropenia such as a patient with a neutrophil count less than 500 cells/microL in the last week who presents to the emergency department with a fever should be immediately evaluated and started on broad–spectrum antibiotics, even if well appearing. A delay of more than 60 minutes in antibiotic administration to patients with severe neutropenia is associated with an increase in morbidity, mortality, and length of stay.