Dr. Ron’s Research Review – September 25, 2013

© 2013

This week’s research review focuses on the hematology of celiac disease.

Anemia secondary to malabsorption of iron, folic acid, and/or vitamin B12 is a common complication of celiac disease and many patients have anemia at the time of diagnosis. Celiac disease may also be associated with thrombocytosis, thrombocytopenia, leukopenia, venous thromboembolism, hyposplenism, and IgA deficiency. (Halfdanarson, Litzow et al. 2007)

Elevated red cell distribution width (RDW) was more common than iron-deficiency anaemia, and is considered a new predictor of celiac disease. (Brusco, Di Stefano et al. 2000) (Sategna Guidetti, Scaglione et al. 2002)

Prolonged prothrombin time (PT) was present in about 20% of adult untreated celiac patients, and was significantly related to all the markers of severe malabsorption, including low mineral density. (Cavallaro, Iovino et al. 2004)

Mean platelet volume (MPV) was found to be increased in celiac disease, and decreased with a gluten-free diet. (Purnak, Efe et al. 2011)

Dr. Ron


Articles

Increased red cell distribution width and coeliac disease

            (Brusco, Di Stefano et al. 2000) Download

BACKGROUND/AIMS: Despite availability of sensitive screening tests, coeliac disease is still underdiagnosed. To determine which haematochemical abnormalities might be more predictive of this condition, we reviewed the clinical records of our series of adult patients affected by coeliac disease. METHODS: Six haematochemical parameters (haemoglobin, red cell distribution width, serum levels of iron, albumin, calcium and potassium) were evaluated in 126 consecutive adult untreated coeliac patients diagnosed since 1990. RESULTS: Elevated red cell distribution width was the most frequent haematochemical abnormality, being present in 57.9% of our patients (Chi square analysis, p<0.01 versus other laboratory changes). CONCLUSION: The increase of red cell distribution width was more common than iron-deficiency anaemia, a well-known indicator of coeliac disease. Elevated red cell distribution width can thus be considered a new predictor of coeliac disease and in the presence of this a search should be made for antiendomysial antibodies.

Prevalence and clinical associations of prolonged prothrombin time in adult untreated coeliac disease

            (Cavallaro, Iovino et al. 2004) Download

INTRODUCTION: Untreated coeliac disease may induce malabsorption of many nutrients. It may also induce vitamin K deficiency, which causes prolongation of the prothrombin time. The aim of the present study was to evaluate the prevalence and associations of prolonged prothrombin time in a series of coeliac adults. METHODS: We carried out a cross-sectional analysis of data collected on 390 adults with untreated coeliac disease diagnosed from January 1997 to December 2000. Prolonged prothrombin time was defined as INR > or = 1.4. RESULTS: A prolonged prothrombin time was found in 72 coeliac patients (18.5%). Parenteral vitamin K therapy was required in 5.6% of patients. Patients with prolonged prothrombin time had significant lower values of haemoglobin, iron, proteins, cholesterol and serum aspartate transaminase, and significantly higher prevalence of diarrhoea, weight loss, abdominal pain and low bone mineral density in comparison with patients with normal prothrombin time. However, low bone density was present in 11.6% of patients with normal INR. A prolonged prothrombin time was only found in a few patients with subclinical coeliac disease (0.9%). CONCLUSIONS: Data indicate that the prevalence of prolonged prothrombin time is about 20% in a large series of adult untreated coeliac patients. A prolonged prothrombin time was significantly related to all the markers of severe malabsorption, including low mineral density. Our suggestion is that vitamin K related proteins may also play a role in determining or worsening calcium homeostasis disorders in coeliac disease. The very low prevalence of coagulation disorders in subclinical coeliac disease indicates that there is no need to screen for coeliac disease in patients with isolated coagulation disorders.

Hematologic manifestations of celiac disease

         (Halfdanarson, Litzow et al. 2007) Download

Celiac disease is a common systemic disorder that can have multiple hematologic manifestations. Patients with celiac disease may present to hematologists for evaluation of various hematologic problems prior to receiving a diagnosis of celiac disease. Anemia secondary to malabsorption of iron, folic acid, and/or vitamin B12 is a common complication of celiac disease and many patients have anemia at the time of diagnosis. Celiac disease may also be associated with thrombocytosis, thrombocytopenia, leukopenia, venous thromboembolism, hyposplenism, and IgA deficiency. Patients with celiac disease are at increased risk of being diagnosed with lymphoma, especially of the T-cell type. The risk is highest for enteropathy-type T-cell lymphoma (ETL) and B-cell lymphoma of the gut, but extraintestinal lymphomas can also be seen. ETL is an aggressive disease with poor prognosis, but strict adherence to a gluten-free diet may prevent its occurrence.

Anemia in celiac disease is multifactorial in etiology

            (Harper, Holleran et al. 2007) Download

Anemia in celiac disease (CD) has been attributed to nutritional deficiencies; however, the clinical manifestations of CD have changed with nongastrointestinal presentations predominating. We collected hematologic parameters from a cohort of patients seen at a tertiary care center for CD to assess the characteristics of anemia in this population. Hematological parameters measured <or=3 months of diagnosis and degree of villous atrophy from 405 patients diagnosed >1995 was analyzed. Ferritin levels were compared with population controls (NHANES III). Iron deficiency was common, occurring in 33% of men and 19% of women (P < 0.001). Folate deficiency was seen in approximately 12% of the total sample and B12 deficiency in approximately 5%. Anemia was present in approximately 20% of the cohort. Among the anemic patients, ferritin was less than the 10th percentile in 45%, between the 10th and 50th percentile in 39% and greater than the 50th percentile in 13%. Ferritin > 50th percentile was more common in anemic men (24%) than in anemic women (9%; P > 0.20). Macrocytic anemia with concurrent B12 or folate deficiency was rare (3%). Elevated ESR was observed in patients with ferritin < 10th percentile and >50th. A gluten-free diet resulted in increased serum ferritin in iron-deficient patients, and decreased ferritin levels in those with high ferritin (r(2) = 0.46, P < 0.001). Although anemia is still a common presentation of celiac disease, nutritional deficiencies alone do not explain this phenomenon in all cases; inflammation appears to contribute as evidenced by the presence of anemia of chronic disease in some individuals.

Mean platelet volume could be a promising biomarker to monitor dietary compliance in celiac disease

            (Purnak, Efe et al. 2011) Download

Abstract Background. Celiac disease (CD) is an autoimmune disease that develops in patients with a genetic predisposition, incurring a susceptibility to gluten-containing foods such as barley, wheat, and rye. The elimination of gluten from the diet is the main therapeutic approach and usually leads to clinical and laboratory improvement. There are no ideal markers that objectively assess dietary compliance in CD patients. Materials and methods. Sixty newly diagnosed CD patients (male/female: 43/17) and 40 healthy subjects (male/female: 23/17) were enrolled in this study. The diagnosis of CD was established by both histological findings of duodenum biopsy (total villous atrophy and lymphocytic infiltration) and positive antibodies against endomysium or gliadin. Results. A significantly higher mean platelet volume (MPV) was observed in the CD group compared with healthy subjects (8.45 +/- 0.96 fL versus 7.93 +/- 0.63 fL; p = 0.004). After introduction of a gluten-free diet, the MPV of CD patients in the dietary adherent group was significantly lower than that of the non-adherent group (8.09 +/- 0.6 fL versus 8.9 +/- 1.08 fL; p = 0.001). Overall dietary adherence rate was 71.6% (43/60 CD patients). In the dietary compliant group, initiation was associated with a significant decrease in MPV from base-line values (8.56 fL versus 8.25 fL; p = 0.008). In the non-adherent group, MPV on 3-month follow-up was higher than at base-line (8.05 fL versus 8.91 fL; p = 0.001). Conclusion. MPV could be a promising and easily available biomarker for monitoring of dietary adherence in CD patients at a low cost in comparison with other modalities.

Coeliac disease and aplastic anaemia: a specific entity?

            (Salmeron, Patey et al. 2009) Download


Red cell distribution width as a marker of coeliac disease: a prospective study

            (Sategna Guidetti, Scaglione et al. 2002) Download

BACKGROUND: Coeliac disease is frequently underdiagnosed because of its protean presentations. Serological tests may be helpful in screening programmes for populations at risk, but they are costly. AIM: To determine prospectively whether a commonly available haematological test such as the red cell distribution width (RDW) could be of help in detecting unrecognized coeliac disease. METHODS: Of 353 consecutive adult patients referred to our outpatient malabsorption clinic, 198 in whom clinical suspicion was strong were referred for further investigations and intestinal biopsy. Seventy-six inflammatory bowel disease outpatients and 90 subjects admitted for diseases other than malabsorption were enrolled as the control group. RESULTS: RDW was increased in 94 (47.4%) and normal in 104 (52.5%) of 198 patients. Duodenal biopsy confirmed coeliac disease in 80 (85.1%) of the former patients and 69 (66.3%) of the latter patients. No correlation between RDW values and histological scores was found. Overall RDW increase was found in 80/149 (53.7%) patients with a definite diagnosis of coeliac disease, and in 14/49 (28.6%) patients in whom biopsy excluded the disease. A 1-year gluten withdrawal led to a significant decrease in RDW value, even in patients with obdurate mucosal impairment. CONCLUSIONS: In patients in whom there is a strong clinical suspicion of coeliac disease, an elevated RDW despite normal haemoglobin concentration may be a reliable predictor of the disease.


References

Brusco, G., M. Di Stefano, et al. (2000). "Increased red cell distribution width and coeliac disease." Dig Liver Dis 32(2): 128-30. [PMID: 10975787]

Cavallaro, R., P. Iovino, et al. (2004). "Prevalence and clinical associations of prolonged prothrombin time in adult untreated coeliac disease." Eur J Gastroenterol Hepatol 16(2): 219-23. [PMID: 15075998]

Halfdanarson, T. R., M. R. Litzow, et al. (2007). "Hematologic manifestations of celiac disease." Blood 109(2): 412-21. [PMID: 16973955]

Harper, J. W., S. F. Holleran, et al. (2007). "Anemia in celiac disease is multifactorial in etiology." Am J Hematol 82(11): 996-1000. [PMID: 17636474]

Purnak, T., C. Efe, et al. (2011). "Mean platelet volume could be a promising biomarker to monitor dietary compliance in celiac disease." Ups J Med Sci. [PMID: 21679011]

Salmeron, G., N. Patey, et al. (2009). "Coeliac disease and aplastic anaemia: a specific entity?" Br J Haematol 146(1): 122-4. [PMID: 19438483]

Sategna Guidetti, C., N. Scaglione, et al. (2002). "Red cell distribution width as a marker of coeliac disease: a prospective study." Eur J Gastroenterol Hepatol 14(2): 177-81. [PMID: 11981342]