VA Resident Report: What is the association between squamous cell carcinoma and acquired factor VIII?

Following surgery for the patient in this case study, the tumor nor the coagulation inhibitor has recurred after 6 months’ follow-up. While it is possible that the inhibitor may have remitted spontaneously or remained in remission because of the therapy given before surgery, the inhibitor’s appearance as the tumor grew and the remission of the tumor as well as of the inhibitor after surgery suggest a causal relationship. As with other factor VIII inhibitors seen with other types of malignancy, it is very unlikely that the tumor was producing the antibody but rather that the tumor induced an autoimmune reaction in the patient.

Shastri, K., Logue, G., Zeid, M., Behrens, A., Lenahan, E., & Haar, J. (n.d.). Acquired factor VIII inhibitor with squamous cell cancer of the epiglottis. Archives of Otolaryngology–head & Neck Surgery., 116(3), 350-353.

A variety of malignancies have been associated with acquired factor VIII inhibitors, including lymphoproliferative diseases6-7 and solid tumors such as those of lung,8 prostate,9 colon,5 and kidney.5 The patient described here developed the acquired inhibitor in conjunction with head and neck carcinoma, specifically squamous cell carcinoma of the epiglottis. This specific association has not been previously reported, to our knowledge. Approximately 12 weeks before the discovery of the head and neck malignancy, the patient had a normal coagulation profile. When the malignancy was discovered, her APTT had risen to approximately twice the normal. Further in vitro testing, described above, documented an IgG antibody that inhibited factor VIII function.


VA Resident Report: How does B12 deficiency cause pancytopenia?

The Bottom Line: A common etiological factor is nutritional deficiency anemia, especially megaloblastic anemia. It accounted for 40 (19.51%) patients presenting with pancytopenia. Megaloblastic anemia due to vitamin B12 deficiency is well recognizable cause of pancytopenia. Various study reported the range of pancytopenia in megaloblastic anemia to be varying from 11-47%.

Zeb Jan, A., Zahid, B., Ahmad, S., & Gul, Z. (n.d.). Pancytopenia in children: A 6-year spectrum of patients admitted to Pediatric Department of Rehman Medical Institute, Peshawar. Pakistan Journal of Medical Sciences., 29(5), 1153-1157.

Pancytopenia is a malady in which there is lessening of all the three cellular elements of blood; prevailing when the hemoglobin (Hb) <10g%, absolute neutrophil count (ANC) <1.5*109/L, platelet count <100*109/L. The pancytopenia was labeled as severe if patient had two or more of the following: Hb <7 gm%, ANC <0.5*109/L, and platelet count <20*109/L.1 In pancytopenia the marrow is customarily hypocellular as a result of primary production defects, it can be due to diminution of hemopoitic cell production, ineffective haemopoiesis or may be due to peripheral devastation of cells

VA Resident Report: Are there cases in the United States of malaria transmitted via blood transfusions?

The Bottom Line: CDC received 1,925 reported cases of malaria with an onset of symptoms in 2011 among persons in the United States, including 1,920 cases classified as imported, one laboratory-acquired case, one transfusion-related case, two congenital cases, and one cryptic case. The total number of cases represents an increase of 14% from the 1,691 cases reported for 2010 and the largest number of reported cases since 1971.

Cullen, K., & Arguin, P. (n.d.). Malaria surveillance–United States, 2011. Morbidity and Mortality Weekly Report. MMWR., 62(5), 1-17.

Transfusion Transmitted Infection
Case. In April, a man aged 76 years who was a veteran was admitted to a military hospital for presumed urosepsis. He had a 1-day history of fevers and, although he had been admitted several times during the previous 6 months for other conditions, had not complained of any symptoms consistent with acute malaria. A hematologist identified malaria parasites incidentally while performing a manual differential of a complete blood count, and the species was subsequently confirmed by PCR to be P. malariae. The patient was treated with an oral antimalarial regimen and recovered fully. The patient’s travel history included a 1- year tour of duty in Vietnam and a short stay in Brazil, both in the early 1970s. The patient had no recent travel to malaria-endemic regions. The patient had been treated for anemia of chronic disease for several years and since December 2010 had been transfused with eight units of red blood cells. The blood bank was contacted and a trace-back investigation was initiated using banked serum samples from the eight donors. One of the donor serum samples had elevated titers against P. malariae and P. falciparum, indicating a previous infectious exposure at an indeterminate time. The implicated donor was contacted and his travel history and malaria exposure was ascertained. The donor lived in Liberia for the first five years of life (1990-1995) with no other travel history.

Review of advancements in treating Multiple Myeloma (MM)

The Bottom Line: New diagnostic criteria, a Revised International Staging System, and the approval of three drugs (four others pending approval) have greatly advanced the treatment, diagnosis, staging, risk-stratification and management of MM. These changes, as well as others detailed in this article, have altered how MM and smoldering multiple myeloma (SMM) are defined.

Reference: Rajkumar, S. Vincent. Myeloma today: Disease definitions and treatment advances. Am J Hematology. 2015 Nov 13; (Accepted article). doi: 10.1002/ajh.24236.

Summary: This review article takes you through the advancements in great detail, including an explanation of the old regimen and how the advances came to be. New diagnostic criteria involve three biomarkers: bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain ratio ≥100, and >1 focal lesion on magnetic resonance imaging.

The Revised International Staging System “combines markers of tumor burden (albumin, beta-2 microglobulin) with markers of aggressive disease biology (high risk cytogenetics and elevated serum lactate dehydrogenase).”

The approval of  carfilzomib, pomalidomide, and panobinostat (elotuzumab, daratumumab, and ixazomib are pending approval) combined with the older agents (cyclophosphamide, dexamethasone, thalidomide, bortezomib, and lenalidomide)  “dramatically increases the repertoire of regimens” available for treatment at each stage.

Administration of hypotonic saline

There are no level II trials examining the use of hypertonic saline in hyponatraemia. One study used a prolonged infusion of 3% HS in seven patients with severe neurological complications from hyponatraemia. Another controlled hyponatraemic seizures with 50 mL of 29.2% HS in five patients. In a prospective study, 33 patients were successfully and safely treated symptomatic hyponatraemia with a prolonged infusion (average of 17 h) of 5% HS.

Banks, Colin J, and Jeremy SFuryk. “Review article: hypertonic saline use in the emergency department.” Emergency medicine Australasia 20.4 (2008):294-305.

Recommendations from recent reviews are to raise serum sodium by 1–2 mmol/L/h while symptomatic with a maximal rise of 8–10 mmol/L over the first 24 h. This should avoid the devastating complication of ODS. 1–2 mL/kg/h of 3% HS has been suggested to raise the serum sodium by 1–2 mmol/h.131 Some authors advocate even higher doses in the setting of seizures or profound obtundation.

Hyponatremia in Dynamed, under treatment

jkn 2/16

What are the mechanisms for coagulopathy and thrombophilia in patients with cirrhosis?

From Cirrhosis and its complications.  In:  Harrison’s Internal Medicine, 18th ed.

Under Major Complications, toward the bottom of the page.

Explains that patients with cirrhosis experience a decrease in production of clotting factors and diminished clearance of anticoagulants.  Portal hypertension may result in hypersplenism which is associated with thrombocytopenia.  Also, diminished vitamin K absorption (as in patients with chronic cholestatic syndrome or decreased hepatic mass) can interfere with production of some of the vitamin k-dependent clotting factors.

Regarding hypercoagulability, most studies seem to address portal vein thrombosis rather than a risk for any thrombosis.

Tripodi A, et al.  Hypercoagulability in cirrhosis: causes and consequences.  Journal of Thrombosis and Haemostasis, 2011; 9: 1713–1723.

This review identifies three case-control studies that look at the risk of VTE in hospitalized patients:  1) 625 cases with VTE & severe liver disease v. 625 controls – reduced risk of VTE in patients with severe liver disease; 2)  6500 cases VTE v. 10,000 controls – non-significant risk of VTE (RR 1.65) in patients with chronic liver disease.  The third study aimed to assess risk of VTE in patients with cirrhosis; 963 patients with cirrhosis v. 12,405 hospitalized patients without cirrhosis.  Incidence of DVT/PE in cases was 1.8% v. 0.9% in controls.  In multivariate analysis, the presence of cirrhosis was not associated with an increased risk in DVT/PE (OR, 0.87).  The article does discuss mechanisms for hypercoagulability that has been observed in plasma taken from cirrhotic patients.

Urine sodium levels in hypovolemic and euvolemic patients

“Spot urine sodium and FeNa+
1. Since hypovolemia promotes avid sodium reabsorption, hypovolemia is usually associated with a low urinary sodium concentration (< 20–30 mEq/L) and low FeNa+(< 0.5%). On the other hand, euvolemic patients do not have a stimulus to reabsorb urine sodium and usually have a higher urinary sodium (> 20–30 mEq/L) and FeNa+.”
Stern SDC, Cifu AS, Altkorn D. Symptom to Diagnosis: An Evidence-Based Guide. 3rd edition. New York, NY: McGraw-Hill Medical; 2015. Available here.

In patients with suspected PE, what is the accuracy of VQ scan compared to chest CT in a patient with suspected PE?

Bottom line:  CT chest provides greater accuracy for diagnosis of acute PE than V/Q scan. some patients may not be able to tolerate CT or have contrainidications to the test, and V/Q scan is a very reasonable alternative testing strategy.  While CT has a slightly higher positive LR, the pooled sensitivity is around 86%, meaning that around 15% of patients with a PE may have a negative CT.

Summary: Pulmonary Embolism, Diagnosis section. In: DynaMed.
Based on systematic review of 12 studies that evaluated CT scan, V/Q scan or both compared to reference standard of pulmonary angiography for diagnosis of pulmonary embolism.

RESULTS:  CT:  Sensitivity – 86%; Specificity – 94%.
V/Q high probability scan:  Sensitivity – 39%; Specificity – 97%
V/Q low probability or near-normal scan:  Sensitivity – 98%; Specificity – 5%

CT and high-probability V/Q scans had similar positive LRs (14.0 and 13.2), but CT scan had better negative LR (0.15) than normal or low-probability V/Q scan (0.4 2.)  However, a normal V/Q scan does have a very good negative LR (0.04, based on PIOPED I data), but this result occurs rarely.