Red cell indices and peripheral blood film findings of anti-Psychotic treatment and treatment naïve Psychiatic patients in a tertiary Hospital in Nigeria

Background: The overall burden of morbidity and mortality from psychiatric disorders is on the rise. Holistic approach in the care of this group of patients has become inevitable. There is need for collaboration between psychiatrists and other physicians, laboratory physicians inclusive. Study design: cross sectional descriptive casecontrol study. Materials and method: A total of 198 patients including controls were recruited for this study. Patients with schizophrenia constituted majority of the respondents, 86.4% of antipsychotic-naïve patients and 90.9% of patients on antipsychotics. A comprehensive medical examination was carried out on every participant. On every sample, automated Full Blood Count was performed using Sysmex2000i and peripheral blood film was made and examined. Result: 51.5% and 47% of anti-psychotropicnaïve patients and patients on anti-psychotic were 18-40 and 41-60 years respectively. Male (57.6%), predominated the anti-psychotic naïve group while female (51.5%) predominated the group on anti-psychotics. Schizophrenia was the diagnosis in the majority of patients, 86.4% and 91% respectively in anti-psychotic naïve and antipsychotic treatment groups. Other diagnoses were depressive illness, substance use disorder and dementia. Of all the subjects, one (1.5%) schizophrenic patients and two (3%) of controls had abnormal haemogram results. For the schizophrenic patient with abnormal results, haematocrit was 12g/dl, MCV of 75fl and MCH of 26pg, while the two controls with abnormal results had only haematocrit deranged with value of 12.3g/d. Neutrophil hypersegmentation was seen on the film of five antipsychotic-naïve patients (7.5%) diagnosed with Schizophrenia and one (1.5%) of the controls. Macrocytosis was only seen in three (4.5%) of the five antipsychotic-naïve patients that had neutrophil hypersegmentation. Conclusion: No significant difference was noted in the Full Blood Counts among the two sets of patients and controls, although there were isolated cases of neutrohil hyperesegmentation and macrocytosis. Keywards: psychiatric disorders; Schizophrenia; Macrocytosis Correspondence to: Dr Shittu AO, Department of Haematology, University of Ilorin, PMB 1515, Ilorin, Nigeria. Email: drakeem06@yahoo.com 1. AO Shittu, Department of Haematology, University of Ilorin. 2. AO Adewoye, Department of Haematology, General Hospital, Katsina. 3. HO Olawumi, Department of Haematology, University of Ilorin. Bangladesh Journal of Medical Science Vol. 18 No. 02 April’19. Page :196-205 DOI: https://doi.org/10.3329/bjms.v18i2.40685


Introduction:
The overall burden of morbidity and mortality from psychiatric disorders is on the rise and is becoming a global public health concern 1 . Psychiatric disorders (PDs) have been greatly underscored as causes of disability, but they account for five out of 10 leading causes of disability 2 . Holistic approach to mental health care has therefore become inevitable 3 . For this approach to be implemented there is need for collaboration between psychiatrists and other physicians, laboratory physicians inclusive. The importance of laboratory medicine has recently been re-emphasized with advances in biological psychiatry 4 . The laboratory methods available now not only confirm diagnosis, but also help to regulate dosage of medication and response to treatment. Diagnoses of psychiatric disorders are made from both clinical and laboratory features. The clinical features include depression, social withdrawal, Hostility or suspiciousness, extreme reaction to criticism, Deterioration of personal hygiene to mention but a few, while the laboratory ones range from low haematocrit, macrocytosis, anisocytosis, poikilocytosis, elevated Mean Corpuscular Volume (MCV), low serum cobalamin and low red cell folate with megaloblastic erythropoeisis in the bone marrow. It has been reported that clinical features may precede haematological ones for several years 5 . Even within haematological features, low serum cobalamin symptoms may occur in the absence of anaemia and macrocytosis. This is because when nutritional deficiency is on-going in the body, cobalamin levels in the neuronal tissues falls much earlier than that in the serum 5,6,7 . These facts explain why routine laboratory tests are unreliable for the diagnosis of PDs 5,7 . In view of these, the highly sensitive serum Metyhlmalonic acid (MMA) and Homocystein levels used in detecting cobalamin deficiency and deficiencies of both cobalamin and folate respectively would be more appropriate in the investigations of patients with PDs, but the bottlenecks associated with laboratory analysis of MMA and homocystein 8,9 have limited their routine use in the diagnosis of cobalamin and folate deficiencies-hyperhomocysteinaemia is seen in variety of other disorders like chronic renal failure, alcoholism, smoking and a highly expensive reagents for MMA assay. Although haematological parameters are not part of the diagnostic criteria for PDs, they may serve as baseline for monitoring treatment and disease progression or as a pointer to an organic basis for PDs. For example, neutropenia has been shown to contribute to immunological factors in the pathogenesis of Obsessive Compulsory Disorders 10 . Neutropenia has also been frequently observed with the use of clozapine 11 . Thrombocytopenia and raised MCV has been observed with the use of sodium valproate dosage level above 80µg/mol especially in females 12 . Auto-erythrocytic sensitization syndrome, a rare mental health problem, characterized by painful and spontaneous purpura especially in female psychiatric patients can be ruled out with Full Blood Count and peripheral blood film examination findings. There have been conflicting reports on red cell indices and peripheral blood film findings in patients with PDs. The aim of this study was therefore to assess the Full Blood Count and peripheral blood findings of these groups of patients and compare our results with that of other researchers.

Routine blood donors who were certified fit
to donate blood and assessed to be free of psychiatric ailments using General health Questionnaire-12 (GHQ-12) served as case controls. GHQ-12 is a 12 item versions and self administered questionnaire used to screen for psychiatric morbidity. Its use has been validated in this environment, with a cut-off of 3 13 . Sample Technique: a multi-staged technique where all newly presenting antipsychoticnaïve patients who certified inclusion criteria were recruited until the required number was obtained. For those on antipsychotics for followup, only those registered with even numbers were recruited for the study. The reason for this was because our data showed that patients on follow-up out-numbered newly presenting ones several folds. Equal number of controls was also recruited for the study. Inclusion criteria for study population 1. Adult newly diagnosed antipsychotic naïve psychiatric patients aged 18-65 years who met ICD-10 criteria 14  Every participant was given a number to ensure confidentiality. All pieces of information were kept confidential. There was no harm to participants except for slight discomfort during venepuncture. No financial burden on the participants and no purnitive measure against those that declined to participate in the study. Methodology: a comprehensive medical examination was carried out on every patients and controls who certified inclusion criteria. Four milliliter of venous blood was obtained aseptically and dispensed immediately into bottle containing EDTA. Automated Full Blood Count was performed on the sample using Sysmex 2000i. Peripheral blood film was made and film stained with May-Graunwald-Giemsa after been air dried. Every film was examined under microscope and morphology of red cells white blood cells and platelets reported. Data Analysis: Data entry and analysis was done using EPI info version 3.5.1. Results were presented in tabular forms. Chi-square was used to compare two variables while continuous variables were compared using correlation analysis. P-value of <0.05 was regarded as been statistically significant.

Results:
Socio-demographic pattern: About half (51.5%) and slightly lower (47%) of anti-psychotropicnaïve patients and patients on anti-psychotic respectively were young adults, while slightly more (53%) of patients on antipsychotics were middle aged. Two (3%), each of anti-psychotic naïve patients and controls were above 60 years of age, Table 1. Male (57.6%), predominated the anti-psychotic naïve group while female (51.5%) predominated the group on anti-psychotics, Table 1. Schizophrenia was the diagnosis in the majority of patients, 86.4% and 91% respectively in antipsychotic naïve and anti-psychotic treatment groups. Other diagnoses were depressive illness (6.1% of anti-psychotic naïve and 4.5% of patients on anti-psychotics), substance use disorder (3% of anti-psychotic naïve and 4.5% of patients on anti-psychotics) and dementia in 1.5% of anti-psychotic naïve patients, Table 2. Haemogram: Of all the subjects, only three had abnormal haemogram results, 1(1.5%) schizophrenic patients and 2 (3%) of controls. Other subjects had haemogram results within the normal reference range, p-value>0.05. For the schizophrenic patient with abnormal results, haematocrit was 12g/dl, MCV of 75fl and MCH of 26pg, while the two controls with abnormal results had only haematocrit deranged with value of 12.3g/dl, Tables 3 and 4. Peripheral Blood Film: Neutrophil hypersegmentation was seen on the film of 5 antipsychotic-naïve patients (7.5%) diagnosed with Schizophrenia and one (1.5%) control, p-value >0.05. Macrocytosis was only seen in 3 (4.5%) of the 5 antipsychotic-naïve patients that had neutrophil hypersegmentation, p-value >0.05, Table 5.        19 were reported. Although no significant difference was noticed in the red cell indices of our patients and controls, positive morphological findings on blood film were noted in few isolated cases. While request for haemogram should always serves as one of the starting points in the management of psychiatric patients, findings of normal haemogram as in this study does not completely rule out the presence of megaloblastic erythopoeisis.

Conclusion:
There is no significant difference in any of the parameters of Full Blood Counts among the two sets of patients and controls, although there are isolated and insignificant number of cases of neutrohil hyperesegmentation and macrocytosis.

Reccomendation:
Since macrocytosis and neutrophil hypersegmentation are early signs in megaloblastic anaemia, their presence in newly diagnosed patients can be a pointer to a low level of RBC folate. It is therefore advisable to always request for blood film review in newly diagnosed psychiatric patients, especially those with schizophrenia.