Blood Tests for Raynaud's Phenomenon
For patients presenting with Raynaud's phenomenon, the essential blood tests include complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibody (ANA), and biochemical profile to distinguish primary from secondary Raynaud's and identify underlying connective tissue diseases. 1
Core Laboratory Panel
The initial laboratory evaluation should include:
- Complete blood count (CBC) with platelet count to detect anemia, thrombocytosis, or other hematologic abnormalities 2, 1
- Erythrocyte sedimentation rate (ESR) - normal in primary Raynaud's but elevated in secondary forms, particularly with connective tissue diseases 2, 3, 4
- C-reactive protein (CRP) to assess for inflammatory conditions 1
- Antinuclear antibody (ANA) - the most critical screening test, as positive results suggest underlying connective tissue disease 2, 1, 3
- Biochemical profile including renal and hepatic function 1
- Thyroid function tests to exclude thyroid-related causes 1
Specialized Autoimmune Testing
When ANA is positive or clinical suspicion for connective tissue disease is high:
- Rheumatoid factor to evaluate for rheumatoid arthritis 2
- Anticentromere antibodies - highly specific for limited systemic sclerosis 4
- Anti-topoisomerase (Scl-70) antibodies - associated with diffuse systemic sclerosis 4
- Anti-U1-RNP antibodies - elevated in mixed connective tissue disease 4
- Lupus erythematosus test for systemic lupus erythematosus 2
Prothrombotic and Vascular Workup
For patients with severe symptoms, digital ulcers, or asymmetric presentation:
- Lupus anticoagulant to detect antiphospholipid syndrome 5
- Anticardiolipin antibodies (IgG and IgM) 5
- Protein C, protein S, and antithrombin III levels to identify clotting system abnormalities 5
- Factor V Leiden and prothrombin mutations in selected cases with thrombotic history 5
- Homocysteine level to detect hyperhomocysteinemia 5
Additional Testing Based on Clinical Context
- Protein electrophoresis to exclude paraproteinemia or cryoglobulinemia 1
- Hepatitis B and C serology when cryoglobulinemia is suspected 1
- HIV testing if risk factors present 5
Key Diagnostic Distinctions
Primary Raynaud's typically shows completely normal laboratory results - normal ESR, negative ANA, and normal CBC. 3, 4 This benign form usually begins at puberty, predominantly affects women, and has symmetric involvement of multiple digits. 4
Secondary Raynaud's demonstrates abnormal laboratory findings - elevated ESR, positive ANA (often with specific autoantibodies), and may show anemia or thrombocytosis. 3, 4 This form tends to begin later in life, causes more severe ischemia with potential for digital ulcers or gangrene, and is most commonly associated with systemic sclerosis. 5, 6
Critical Pitfalls to Avoid
Do not rely solely on laboratory tests - nailfold capillaroscopy is essential and can detect systemic sclerosis years before other manifestations appear. 1, 3 Normal capillaroscopy with negative ANA strongly suggests primary Raynaud's, while abnormal capillaroscopy (enlarged capillaries, hemorrhages, avascular areas) indicates secondary disease even if other tests are initially normal. 3, 4
Timing matters - blood samples should be collected before initiating any immunosuppressive therapy to avoid false-negative results. 7 Additionally, acute stress, inflammation, or pregnancy can falsely elevate certain markers. 8
Age and presentation guide testing intensity - older age at onset (>30 years), unilateral or asymmetric involvement, severe painful episodes, digital ulceration, or systemic symptoms (joint pain, skin changes, dysphagia) warrant comprehensive autoimmune and prothrombotic evaluation. 5, 6