Anemia / Low blood count and rheumatic disease 4.27/5 (15)

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ICD-10 D64.9 (unspecified anemia)


In anemia, there is a low hemoglobin concentration in the blood ("low blood percentage") or too few red blood cells (blood cells, erythrocytes). The condition is not uncommon in chronic rheumatic inflammatory diseases such as systemic connective tissue diseases, vasculitis and arthritis. This is due to a link between chronic inflammation and anemia (inflammatory anemia) (Weiss G, 2019).

Other causes of anemia in rheumatic disease are iron deficiency and more rare conditions. Many of these are discussed below. The condition leads to reduced uptake and transport of oxygen to the cells in the body and thus reduced endurance.

Reference areas (normal hemoglobin): above 11.5 g / dl in women, above 13,5 g / dl in men. Africans of both sexes have 0,5 to 1.0 g / dL lower hemoglobin.

Causes of anemia in rheumatic disease

This image is missing alt text; its filename is Anemia-By-James-Heilman-MD-Own-work-BY-SA-3.0wikimedia.org_.jpg
Anemia in the hand to the left Illustration James Heilman, MD - Own work, CC BY-SA 3.0,

Chronic inflammatory diseases which in long-term rheumatic disease causes anemia (inflammatory anemia). This often follows the disease activity (for example measured by CRP). Often in these diseases the production of hemoglobin is too low, the blood cells do not mature or live shorter, which is seen in Rheumatoid arthritis (arthritis), Systemic lupus erythematosus (SLE), Juvenile arthritis, Still's disease and other diseases with chronic autoimmune inflammation including Crohn's disease and ulcerative colitis, but also in chronic infections such as HIV, Tuberkulosis (Tbc), Epstein-Barr virus, Parvovirus B19 and cancers, vitamin deficiency (vitamin B12, folic acid / folate / vitamin B9).

Disease located in the bone marrow (where the blood cells are produced). Leukemia, Multiple myeloma and other cancers of the bone marrow. Myelodysplastic syndrome is a collective term for many malignant bone marrow diseases that cause pancytopenia. Myelofibrosis. Fanconi anemia most commonly detected in childhood, some are detected later with low platelets (platelets), anemia with high MCV (macrocytic anemia when MCV is above 100 fL), short stature and pigment changes in the skin (Cafe-au lait, freckles in armpits). Chronic renal failure, erythropoietin (EPO) deficiency, long-term alcohol abuse, aplastic anemia which is divided into congenital and acquired type. Acquired type is caused by autoimmune condition with destruction of hematopoietic stem cells in 60% (Wang L, 2019).

Acute anemia is characterized by rapidly decreasing hemoglobin and can develop by hemolysis (hemolytic anemia, see below), most often by systemic lupus erythematosus (SLE) or by major bleeding, such as from aneurysms or by pulmonary hemorrhage in vasculitis diseases. Bleeding in the lungs may cause falling hemoglobin without any particular other symptoms. Difficulty breathing often develops over time. Such pulmonary hemorrhages occur by granulomatosis with polyangiitis (GPA, Wegener's granulomatosis), less often by SLE og Antifosfolipid syndrome. Behcet's disease may cause ulcers and bleeding in the intestinal tract.

Age. Also among older people, anemia is often related to inflammation, often an infection. In a study of 191 elderly hospitalized people with anemia, 70% had an inflammatory cause, of which 71% had an acute infection. A total of 16% had chronic kidney failure, 12% cancer, 16% chronic infection or inflammatory disease (Joosten E, 2014). 

Obesity is related to low-grade inflammation and in that context increased incidence of anemia.

Hemolytic anemia causes the red blood cells to be destroyed. This can happen when the immune system by mistake attacks, such as by Systemic lupus erythematosus (SLE). Other causes are hot hemolytic anemia, cold agglutinin hemolytic anemia cold agglutinins (including wood mycoplasma pneumonia infection), Epstein-Barr virus (EBV, mononucleosis), clostridium difficult sepsis, paroxysmal cold hemoglobinuria in children with dark, cola-colored urine and abdominal pain (Reference: Kvikstad SAS, 2019), paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli syndrome) in children. TTP (thrombocytopenic purpura), HUS, aHUS (Hemolytic Uremic Syndrome), Rh disease (among newborns) and transfusion reaction (after blood transfusion).

Non-autoimmune hemolytic anemia has a number of causes such as hemolytic uremic syndrome (HUS, aHUS), malaria, transfusion reaction. Glucose-6 phosphate dehydrogenase deficiency, disseminated intravascular coagulation (DIC), dialysis, artificial heart valves, runner anemia / exercise anemia (Hill A, 2018). Hereditary spherocytosis (spherical cell anemia) is the most common congenital hemolytic anemia in Northern Europe (1: 5000). Hereditary elliptocytosis, pyruvate kinase (PK) deficiency and abetalipoproteinemia are other rare causes.

Characteristics of hemolysis: Fever and sweating, rapidly decreasing hemoglobin, MCV normal, LD high, haptoglobin low. Direct antiglobulin test (DAT). If this is positive, a monospecific ("extended") direct anti-globulin test (DAT) is performed. This test examines which immunoglobulin class or complement protein is present on the cell surface.

Cancer in the advanced stage is also associated with inflammation and hence with anemia. Hodgkin's lymphoma, chronic lymphocytic leukemia (CLL) are examples.

Reduced iron uptake from the intestine (malabsorption) occurs in chronic intestinal diseases and when rheumatic disease attacks the intestine, such as in systemic sclerosis.

NSAID (ibuprofen, diclofenac and more) is a common cause of bleeding in the gastrointestinal tract. Such small or larger wounds do not have to cause pain and are then detected by gastroduodenoscopy. Usually there are microscopic amounts of blood in the stool that can also be tested. The risk increases especially with the concomitant use of "blood-thinning drugs" such as Albyl-E, Eliquis, Fragmin, Klexane, Marevan, Xarelto and more.

Other drugs and toxins are cytotoxic drugs, sulfonamides (sulfa), thyrostatics (for high metabolism), colchicine (gout, familial Mediterranean fever), chloramphenicol (not eye drops), lead, benzene (gasoline).

Iron deficiency anemia. Chronic bleeding. In general, iron deficiency is often caused by chronic bleeding during menstruation, gastrointestinal bleeding, helicobacter infection, in wounds, inflammation, tumors (cancer) or after surgery in the form of bleeding anemia. A diet that is one-sided over a long period of time (diet, reduced appetite) can result iron deficiency (microcytic) or anemia due to vitamin B12 - or folic acid / folate (macrocytic). Malabsorption in intestinal disease as seen associated with systemic sclerosis, in celiac disease and inflammatory bowel disease (IBD). Intestinal parasites (hookworm, trichuris trichiura) are rare causes. By systemic sclerosis (scleroderma), diffuse form, bleeding in the stomach can cause anemia over time (weeks).

Conditions similar to iron deficiency (differential diagnoses) thalassemia. This is also a microcytic anemia (low MCV in the blood), but with normal transferrin receptor / ferritin. Also, reticulocytes are elevated. Beta-thalassemia is detected by hemoglobin electrophoresis (high hemoglobin A)2). Alpha-thalassemia is detected by molecular methods. Other hemoglobin variants (most common among people from tropical and subtropical regions): HBE, HbC, HbD-Punjab, HbS, sickle cell anemia.

Genetic diseases. Genetic hemoglobin variants are found in several diseases. Sickle cell anemia and thalassemia are among the most common. In sickle cell anemia, there are symptoms from childhood. The fear is sickle cell crisis with severe pain, tissue death and organ damage. About. 80% with sickle cell anemia are ethnic, sub-Saharan Africa. Thalassemia causes mild-to-severe (microcytic) anemia. alpha and beta classasemia. The severity depends on genetic conditions that can be tested. Men and women are attacked just as often. Most are ethnic from Italy, Greece, the Middle East, South Asia and Africa.

Other causes is alcohol abuse (long-term), bone marrowdisease that causes production deficiency (Fanconi anemia, myelofibrosis). In aplastic anemia, all cell lines (leukocytopenia, thrombocytopenia) attacked. Poisoning (Lead, benzene), chronic renal failure (erythropoietin deficiency), drugs (cytostatics, sulfonamides, thyrostatics, colchicine, NSAIDs). Bleeding is also seen at the fore low platelet count (under 30 x 109/ L).

Pregnancy Anemia is hemoglobin below 11.0. The cause may be dilution by increased fluid in the body in the last trimester, but one must also be aware of the possible lack of vitamins and / or iron. Read more about Pregnancy in rheumatic diseases here


Anemia is often noticeable fatigue and exhaustion, dizziness and increased need for sleep. Heavy breathing and rapid pulse during exercise, cold hands and feet, headaches, sores in the corners of the mouth and hair loss also occur. Hemolytic anemia can acutely cause sweating, fever and abdominal pain.

Examinations for anemia and rheumatic disease

Medical history includes typical symptoms (see above).

Clinical pale skin and mucous membranes may be noticeable and the pulse may be faster than normal (tachycardia). In case of hemolysis / haemolytic anemia (see above) frostbite and fever may occur.

Laboratory tests frequently examined are CRP, hemoglobin, reticulocytes (low number is <20 × 109/ L), MCV (iron deficiency: low MCV / microcytic: <80 fl), MCH and MCHC, soluble transferrin receptor, ferritin below the reference ranges (NOTE! false elevated values ​​in rheumatic inflammation or infection), LD, haptoglobin, Vitamin B12, folic acid. Genetic analysis in case of suspected genetic defect. Helicobacter antibody. In case of suspicion Celiac Disease blood test for anti-TG2 / anti-DGP and tissue test from small intestine may be relevant. Urine sticks.

Other investigations may include a stool sample for traces of blood, calprotectin (Crohn's disease) or parasites (hookworm, trichuris trichiura). Colonoscopy of the colon, capsule endoscopy of the small intestine and gastro-duodenoscopy. Also tissue sample from bone marrow may be relevant in some cases.


The diagnosis is based on symptoms, clinical assessment, laboratory tests and additional assessment (see above).


Treatment of iron deficiency anemia is with the addition of iron. Classic iron tablets (divalent iron) or injections if there is reduced absorption from the intestine. Maintenance with an iron-rich diet and / or (trivalent) hemo-iron or Compiron (via online store or pharmacy).

Treatment of hemolytic anemia is complicated and depends on the underlying cause. Hospitalization and collaboration with a hematologist are recommended


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