Can Vitamin D Deficiency Cause Low Platelet Count

1. Characteristics of study and control groups

This analytical cross-sectional study included 132 patients with pSS (3 men, 129 women; mean age: 52 years, range: 40.7∼63.3 years) recruited from rheumatology outpatient clinic between 2013 and 2016 and 129 age- and gender-matched healthy controls (3 men, 126 women; mean age: 51.6 years; range: 39.8∼64.7 years. A total of twenty-eight patients were excluded from study due to these follow exclusion criteria: inability to obtain informed consent (N=3), incomplete laboratory data (N=13), malignancy (N=2), platelet disorder (N=1), other autoimmune disorder (N=6), use of anticoagulant or anti-platelet agents (N=3). The power analysis was performed to determine sample size that could provide 95% power at alpha level of 0.05 (http://biostat.mc.vanderbilt.edu/twiki/bin/view/Main/PowerSampleSize).

There was no significant difference in N, L, PLT, MPV and ESR values between study and control groups. The PDW was found to be significantly higher in study group than controls (15.58±2.7 fL vs. 12.7±2.41 fL) while no significant difference was found in PCT levels between study and control groups (0.279±0.071 vs.0.320±0.110). No significant difference was detected in CPR levels between study and control groups while vitamin levels were significantly lower in patients with pSS than controls (21±15.7 ng/mL vs. 29.7±15.2 ng/mL; P<0.05). In addition, RF values were significantly higher in patients with pSS than controls (14.02±11.09 IU/mL vs. 3.58±3.26 IU/mL; P<0.05). RF was found to be negatively correlated with vitamin D (P<0.001, r_s=−0.681), plateletecrit (P<0.001, r_s=0.664) and platelet counts (P< 0.004, r_s=0.600) in patients with pSS. No significant correlation was found between vitamin D levels and CRP or ESR in patients with pSS (Table 1).

Table 1

The status of hematologic parameters by groups

Parameters	pSS patients Mean±SD (N=132)	Healthy controls Mean±SD (N=129)	Reference ranges	P values
Vitamin D (ng/mL)	21.0±15.7	29.7±15.2	>30	<0.05
CRP (mg/L)	6.53±5.25	5.25±4.73	0~5	NS
ESR (mm/h)	15.25±4.6	12.17±6.87	0~20	NS
RF (IU/mL)	14.02±11.09	3.58±3.26	0~14	<0.05
Platelet (×10³/μL)	266±53.4	287.2±72.97	150~450	NS
MPV (fL)	9.6±1.71	10.2±2.89	9~12	NS
PDW (fL)	15.58±2.7	12.7±2.41	10~16	0.012
PCT (%)	0.279±0.071	0.320±0.110	0.17~0.4	0.049
PLR	142.047±58.23	128.098±42.51	-	<0.001
Lymphocyte (×10³/μL)	2.14±0.52	2.53±0.68	0.8~3.4	NS
Neutrophil (×10³/μL)	4.33±1.14	4.12±2.12	1.8~7.5	NS

Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; RF, Romatoid factor; MPV, mean platelet volume; PDW, Platelet distribution width; PCT, Plateletecrit; PLR, platelet-to-lymphocyte ratio; NS, no significance.

2. Study group characteristics

In pSS group, only 3 patients were male. Mean age was 52±11.26 years in the study group. Disease duration was estimated as 40±21 months (median, min-max: 36.5∼36.127). Mean time from diagnosis was found to be 19±18 months (median, min-max: 18.5∼19.70). In the study group, sicca symptoms were present in 94% whereas joint involvement in 93% and fatigue in 67% (Table 2). Salivary gland biopsy was performed in 64 patients, revealing diagnostic findings in 61 patients; however, it was non-diagnostic in remaining 3 patients. When auto- antibody profile was considered, it was seen that SS-A and SS-B auto-antibodies were available in all patients. Positive SS-A and SS-B results were found in 78% and 64% of patients, respectively. Anti-DsDNA, RNP, anti-Jo, ANA, SM and Scl70 antibodies were found to be present in 15%, 3%, 98%, 91%, 1% and 4%, respectively (Table 3).

Table 2

Clinical characteristics of patients with Sjögren's syndrome

Characteristics	Mean (min-max or %)
Age (years)	52 (28~72)
Gender (female) (N(%))	129 (3)
Cigarette (yes/no)	29/103
Disease duration (months)	40 (38.6~144.36)
Duration of diagnosis (months)	15 (8.5~50.19)
Articular involvement (N(%))	122 (93)
Sicca symptoms (N(%))	124 (94)
Change in fatigue (N(%))	72 (67)
Neuropathy-lymphoma (N(%))	1 (0.8)
Symptoms on diagnosis
Sicca (N(%))	118~89 (75.4)
Joint (N(%))	112~85 (75.8)
Other (N(%))	20 (15-75)
Treatment
Hdyroxychloroqine (N(%))	118 (89)
Hdyroxychloroqine (N(%))	131 (79)
Methotrexate (N(%))	3 (2.2)

Table 3

Autoantibody profiling and frequency of autoantibodies in patients with pSS

Parameters	Total	No. of positive/negative (FO)
SS-A	132	103/29 (78)
SS-B	132	84/48 (64)
Anti Ds-DNA	100	15/85 (15)
RNP	100	3/97 (3)
Anti-Jo	100	98/2 (98)
ANA	100	91/9 (91)
SM	100	1/99 (1)
Scl70	100	4/96 (4)
SGB	64	61/3 (95)

Abbreviations: FO, Frequency of occurrence(%); SS-A, anti-Sjögren's Syndrome antigen A; SS-B, anti-Sjögren's Syndrome antigen B; Anti Ds-DNA, Anti-double stranded DNA; RNP, Anti-RNP antibody; Anti-Jo, antihistidyl ANA, antinuclear antibody; SM, Smith antigen; Scl70, Anti-Scl70 antigen; SGB, salivary gland biopsy.

In correlation analyses, a significant, negative correlation was found between vitamin D and RF (r_s=−0.681, P< 0.005) while a weak correlation was detected between low vitamin D levels and SSDI scores (r_s=−0.126, P<0.05). Further, the vitamin D correlations were revealed with some platelet indices in patients with pSS (for PDW, r_s=−0.408, P<0.01 and for PCT r_s= 0.646, P<0.001; Table 4).

Table 4

Vitamin D correlations with some demographic and hematologic parameters of patients with primer Sjögren's syndrome

Parameters	Correlation coefficient (rs)	P value
SSDI	−0.126^*	0.047
Platelet(×10³/μL)	0.414	0.075
MPV(fL)	0.419	0.074
PDW(fL)	−0.408^*	0.012
PCT(%)	0.646^**	<0.001
PLR	0.103	0.103
Lymphocyte(×10³/μL)	0.045	0.617
Neutrophil(×10³/μL)	−0.061	0.499
Monocyte	0.102	0.262
Eosinophils	0.015	0.869
Basophil	−0.092	0.309
ESR	0.097	0.495
RF	−0.681^**	0.004
Eosinophils	0.015	0.869

^** Correlation is significant at the 0.01 level (2-tailed),
^* Correlation is significant at the 0.05 level (2-tailed).

Abbreviations: SSDI, Sjögren's Syndrome Damage Index; MPV, Mean platelet volume; PDW, Platelet distribution width; PCT, Plateletecrit; PLR, platelet-to-lymphocyte ratio; ESR, erythrocyte sedimentation rate; RF, Romatoid factor.

The patients with pSS were stratified into 3 groups according to vitamin D levels: group I (severe deficiency) (N=34), group II (deficiency) (N=46) and group III (sufficient) (N=52). Mean vitamin D levels were 6.8±1.8 ng/mL, 16.3±1.7 ng/mL and 21±3.2 ng/mL in group I, II and II, respectively. Mean PDW and PCT values were found to be 17.48±1.74 and 0.259±0.491 in group I; 16.3±1.41 and 0.275±0.028 in group II; and 15.1±1.36 and 0.278± 0.324 in group III, respectively. There was a significant difference in PDW between Group I and III (Figure 1 and Table 5).

Table 5

The status of hematologic parameters by groups

Parameters	Group I Vitamin D <10 ng/ml Mean±SD (N=34))	Group II Vitamin D 10~20 ng/mL Mean± SD (N=46)	Group III Vitamin D >20 ng/mL Mean±SD (N=52)	P values
Vitamin D (ng/mL)	6.81±1.8^{^a,^b}	16.3±1.7^{^a,^c}	21±3.2^{^b,^c}	<0.001
PDW (fL)	17.48±1.74^{^a}	16.3±1.41	15.1±1.36^{^c}	0.024
PCT (%)	0.259±0.491	0.275±0.028	0.278±0.324	0.028

^a Shows the groups which differs according to the Group III.
^b Shows the groups which are different according to Group II.
^c Shows the groups which differs according to the Group I.

Abbreviations: SD, standard deviation; PDW, Platelet distribution width; PCT, Plateletecrit.

Fig. 1.

Subgroup's graph of vitamin D and platelet distribution width.

Univariate and multivariate linear regression analysis was performed. In multivariate linear regression analysis, PDW was a dependent variable and independent variables was adjusted as age, sex, duration of disease, CRP, ESR, PCT, PLR, vitamin D. In the multivariate regression, parameters with significant effect on PDW were as follows: vitamin D (β=−0.373; t=−2.626; sig.=0.013) and platelecrit (β=−0.308; t=−2.13; sig.=0.040).

The ROC curves were constructed for PDW and PCT according to vitamin D level in patients with pSS. Figure 2 presents parameters describing ROC curves. The cut-off points estimated as 12.53 and 0.29 for PCT and PDW. The AUC, sensitivity and specificity were 0.921, 90% and 85% for PDW and 0.660, 68% and 55% for PCT, respectively.

Fig. 2.

Receiver operating characteristic analysis of PDW, and PCT that predict pSS.

3. Control group characteristics

The control group was selected from hospital staff and relatives of patients. The age- and sex-matched controls without history of systemic disease and/or chronic medication were enrolled to the study. In the control group, no significant relationship was found between vitamin D levels and platelet. The vitamin D levels were consistent to those reported for Turkish population (Mean±SD: 29.7±15.2) [23].

Can Vitamin D Deficiency Cause Low Platelet Count

Source: http://www.kjcls.org/journal/view.html?doi=10.15324/kjcls.2018.50.4.484

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Can Vitamin D Deficiency Cause Low Platelet Count