Anaemia with Thrombocytosis

A 49 year old woman presented with weakness and fatigability. On examination, other than pallor of the skin and mucosa there was no other finding.  A haemogram was done that showed a haemoglobin: 6.7g/dL, leucocyte count: 9.1 X 109/L and a platelet: 664 X 109/L.

Anaemia and thrombocytopenia is a feature of

  1. Myeloproloferative neoplasm
  2. Chronic inflammation
  3. Underlying malignancy (Paraneoplastic)
  4. Iron deficiency

A haemogram from a automated haematological counter hides a lot of information. Before more investigations are done it is important to assimilate all the information in the haemogram. The haemogram in the above listed conditions shows:

  1. Myeloproliferative Neoplasm: The myeloproliferative neoplasm are diseases characterised by proliferation of bone marrow. They are distinct from acute leukaemia. According to the 2016 WHO classification myeloproliferative neoplasm include chronic myeloid leukaemia (CML), chronic neutrophilic leukaemia (CNL), polycythaemia vera (PV), progressive myelofibrosis (PMF), essential thrombocytosis (ET), chronic myeloproliferative neoplasm unclassified (CMPN-U) and chronic eosinophilic leukaemia (CEL).  Myeloproliferative diseases associated with anaemia and thrombocytosis are CML, prefibrotic phase of PMF and CMPN-U. Haemogram of patients with myeloproliferative diseases shows leucocytosis with presence of immature leucocyte forms. This is most pronounced in patients with CML. In fact leucocytosis with the presence of immature leucocyte forms is the dominant feature of the haemogram of patients with CML. Anaemia of myloproliferative is normocytic and normochromic.
  2. Chronic Inflammation and Paraneoplastic Diseases: Anaemia and thrombocytosis can also be seen in patients with chronic inflammation and as a paraneoplastic finding. An occasional immature leucocyte form may also be seen in these conditions. This picture may be indistinguishable from that myeloproliferative diseases other than CML. The anaemia is normocytic and normochromic. When the chronic disease or neoplasm is associated with blood loss as may be the case in cancers of the gastrointestinal tract or inflammatory bowel disease, microcytosis due to a coexisting iron deficiency may be seen.
  3. Iron Deficiency: Iron deficiency is associated with microcytic hypochromic anaemia. The degree of microcytosis co-relates with the degree of iron deficiency. The leucocyte counts depends on the cause of iron deficiency. Commonly the leucocyte is normal or slightly decreased. Patients who have iron deficiency because of blood loss due to an inflammatory condition may have leucocytosis. Iron deficiency from blood loss due to helmethiasis may cause eosinophilia.

The differential leucocyte count showed 67% polymorphs, 27% lymphocytes, 2% monocytes and 4% basophils. The erythrocyte indices were MCV 61fl, MCH 15.3pg and MCHC 24.9g/dL. The red cell distribution width was 28.5%. The peripheral smear showed hypochromia, microcytosis, anisocytosis and poikilocytosis.

Of the causes of anaemia and thrombocytosis listed above only iron deficiency is characterised by hypochromic microcytic anaemia. Iron deficiency is also characterised by anisocytosis and poikilocytosis. This manifests as increased red cell distribution on the haemogram.

The serum iron was 27.9 µg/dl, the total iron binding capacity 488 µg/dl with a transferrin saturation 5.7%. The serum ferritin was 8.53 ng/ml. The haemoglobin electrophoresis showed a haemoglobin A2 of 2.8%, the HbA 96% and haemoglobin F 1.2%.

Iron deficiency is diagnosed by documenting low body iron stores and/or impaired iron delivery of iron to the erythroid precursors. The gold standard for depletion of iron stores is absence of stainable iron in the bone marrow. Serum ferritin accurately reflects body iron stores. It has become the preferred method to demonstrate depletion of body iron stores because of the invasive nature of bone marrow aspiration. Levels less than 15ng/ml strongly suggest iron deficiency. Serum ferritin is specific but not sensitive for iron deficiency. Its has a sensitivity of 59% if the cutoff is 15ng/mL and 75% if the cutoff is less than 16ng/ml. The low sensitivity makes the test of limited value to exclude iron deficiency. Ferritin in an acute phase reactant. It has a limited value in the presence of inflammation.

Unlike low serum ferritin, low serum iron is of limited value in diagnosis of iron deficiency. Iron delivery to the haemoglobinizing erythroid precursors is a function of transferrin saturation rather than the serum iron levels. One can have a low serum iron and a low total iron binding capacity as may be seen in anaemia of chronic disease and yet have a normal transferrin saturation. Such patients do not benefit from iron supplementation. Patients with iron deficiency have a low transferrin saturation indicated impaired iron delivery to the developing erythroid cells. Lower the iron saturation higher the probability of iron deficiency being present. Patients are considered to be iron deficient if the transferrin saturation is less than 16%. This patient had a transferrin saturation of 5.7% and a serum ferritin of 8.63ng/ml along with microcytic hypochromic anaemia. A diagnosis of iron deficiency anaemia was made.

The diagnosis of iron deficiency is incomplete without diagnosing the cause of anaemia. Iron deficiency in a 49 year old woman frequently is a result of blood loss that is often menstrual.  This woman had attained menopause and is being evaluated for a gastrointestinal blood loss.

Case 2 – Thrombocytopenia Due to Large Platelets

A 52 year old patient presented with thrombocytopenia discovered on a haemogram performed about 2 years before presentation. The first haemogram performed as a part of a health checkup showed a platelet count of 81 X 109/L with an MPV of 13.1fl. The haemogram had been performed on multiple occasions since then and the platelet count has been reported by different laboratories to be between 63 X 109/L and 103 X 109/L. The haemoglobin, red cell indices, total and differential WBC count was normal.

The patients had no personal or family history of bleeding. He had undergone an appendicectomy and a tooth extraction without excessive bleeding.

The first step in the evaluation of a patient with thrombocytopenia is to confirm if the platelet count is really low. The causes of pseudothrombocytopenia include

  1. Presence of large platelets
  2. Platelet satellitism
  3. EDTA (or rarely other anticoagulant) induced platelet aggregation

The figure below shows the peripheral smear and the platelet histogram of the patients compared to a normal individual.

The platelet count performed manually was 130 X 109/L. The patients was a native of North India. Mild thrombocytopenia (platelet count between 100 X 109/L and 150 X 109L) is found in 26% of blood donors from eastern India and 18% blood donors from northern india (HVK Naina et al. Journal of Thrombosis and Haemostasis 2005; 11:2581-2).

Automated counters have limitations in evaluation of thrombocytopenia. The peripheral smear must be examined in every patient with thrombocytopenia to exclude giant platelets, platelet aggregation and platelet satellitism that may cause thrombocytopenia.