Answers to Anemia Quiz

These synopses are to help you with your private study of the cases. Please do not read them until you have worked through the problems for yourself, or the value of the exercise will be lost.

Case 1: This is an elderly man with a microcytic anemia, and the low serum iron together with the raised TIBC is sufficient to diagnose iron deficiency. A cause in such patients MUST be identified, as many of them will have bleeding GI lesions, including cancers. This man has a history of a change in his bowel habit, and an abdominal mass, and needs investigation of his colon.

Diagnosis: iron deficiency secondary to chronic blood loss from colon cancer

Case 2: This is a woman with a very mild anemia, but with substantial microcytosis. The serum iron, TIBC, and ferritin are normal, excluding iron deficiency. Thalassemia trait is the most likely cause, and in this case the diagnosis is reached by measuring the level of HbA₂, which is elevated. This confirms beta thalassemia trait. Alpha thalassemia trait is harder to diagnose.

The patient herself will have no clinical problems, but genetic counselling is important

Diagnosis: beta thalassemia trait

Case 3: This woman has a severe macrocytic anemia, and also a mild pancytopenia. Possible causes would include vitamin B₁₂ or folate deficiency on the one hand, or more sinister causes of marrow failure such as leukemia, myelodysplasia, or myeloma on the other. Here the story of tingling and a sore tongue suggest vitamin B₁₂ deficiency, and the vitiligo, and family story of thyroid disease indicate the possibility of pernicious anemia. She has a low serum vitamin B₁₂ which confirms this deficiency: the low red cell folate and highish serum folate are typical also of vitamin B₁₂ deficiency.

The diagnosis of pernicious anemia as very likely, and can be confirmed using the Schilling Test. A bone marrow is optional, but would demonstrate megaloblastic change, and this would tell you that vitamin B₁₂ or folate deficiency was the diagnosis before the levels were known.

Diagnosis: pernicious anemia

Case 4: This man has a normocytic anemia in the setting of lung cancer. There are no features on the blood film to indicate marrow infiltration, and it is reasonable to assume that this is the "anemia of chronic disease". No further tests are needed.

Diagnosis: the anemia of chronic disease

Case 5: This is a normocytic anemia, but the dominant feature is a raised leukocyte count, and severe thrombocytopenia. The differential white count shows that most of the leukocytes are blast cells: this is strongly suggestive of acute leukemia, with bone marrow failure. The only necessary test is a bone marrow, and an urgent hematological opinion. Untreated, such patients may die quickly, sometimes within a day or so, depending upon the rate of progression of the disease.

Diagnosis: acute leukemia

Case 6: This is a normocytic anemia occurring in the setting of probable breast cancer. The blood film shows myelocytes, and nucleated red cells, a picture known as "leukoerythroblastic". In turn, this usually indicates the presence of bone marrow replacement eg by fibrosis or cancer. In the setting of breast cancer, a leukoerythroblastic blood picture almost always indicates bone metastases. A bone marrow aspirate and trephine biopsy would confirm this, or a bone scan. The latter is less painful.

Diagnosis: breast cancer with bone metastases

Case 7: This is a normocytic anemia, and the reticulocyte count is raised, indicating possible hemolysis (bleeding will raise the retic count, too). The low haptoglobin and raised indirect bilirubin confirm hemolysis. The history is important. The patient has had episodic jaundice and gallstones: this could be caused by hemolysis and pigment stones. There is a similar history in the mother and brother, which could indicate an autosomal dominant inheritance pattern. The spleen is palpable, as might be expected in long-standing hemolysis, and there is no lymphadenopathy to suggest lymphoma.

The blood film shows spherocytes, and these may be found in hereditary spherocytosis, and in warm autoimmune hemolysis. The negative Direct Coombs' Test excludes the latter, leaving the diagnosis of hereditary spherocytosis. An osmotic fragility curve would be positive, but would not be necessary because the blood film has made a firm identification of spherocytes.

Diagnosis: hereditary spherocytosis

Case 8: An important cause of recurrent joint pain in black people (and other populations where the gene is common) is Sickle Cell Anemia. Sickled red cells are seen on the film, and the laboratory results are consistent with the presence of hemolysis. There is a history of jaundice, and a family history of anemia, joint pains, and gallstones.

Note that the film shows nucleated red blood cells, as may occur in any hemolytic anemia. It also shows Howell-Jolly Bodies, indicating hyposplenism. Most patients with Sickle Cell Anemia undergo "autosplenectomy" due to infarction in the first decade of life.

Hemoglobin electrophoresis will confirm the diagnosis.

Diagnosis: Sickle Cell Anemia

Case 9: Here is a severe microcytosis, and a moderate pancytopenia occurring in a patient with active rheumatoid arthritis. The patient takes NSAIDS, and has indigestion. The spleen is palpable.

The serum iron is low, but so is the TIBC, so one can draw no conclusions about iron status from these. The serum ferritin is normal, but in the context of active inflammation, this does not exclude iron deficiency. Microcytosis can itself result from active inflammation even in the presence of normal iron stores. The only way to achieve a diagnosis of the microcytosis is either with a therapeutic trial of iron (cheap, easy and painless), or a bone marrow (expensive, easy and painful).

The pancytopenia might be a result of "Felty's Syndrome", in which Rheumatoid Arthritis causes splenomegaly and hypersplenism. The setting is so characteristic, that I think one is entitled to make this assumption. On the other hand, to exclude more serious causes such as aplastic anemia (possibly secondary to his medications) or bone marrow neoplasia, a bone marrow aspirate and trephine biopsy would be indicated.

Diagnosis:1. Iron deficiency

2. Felty's Syndrome

3. ? superimposed "anemia of chronic disease" (can't tell at this point)

Case 10: This man drinks a lot of ethanol, and has a macrocytic anemia and thrombocytopenia, both of which can occur with ethanol ingestion. The normal vitamin B₁₂ and red cell folate serve to exclude deficiency of either. In this circumstance, the likelihood of the ethanol being the cause is so high that further investigation, including a bone marrow, is not needed. In the unlikely event that he can be persuaded to stop drinking, the platelets should recover within a week or two, but the MCV will gradually return to normal over about three months.

Diagnosis: ethanol toxicity on bone marrow

Case 11: A complicated hematological case! The anemia is slightly macrocytic, and there is a high leukocyte count, and a low platelet count. The differential shows large numbers of mature lymphocytes, and some "smudge cells", which in a patient of this age makes the diagnosis of Chronic Lymphocytic Leukemia very likely.

The blood film also shows spherocytes, and the reticulocyte count is high. This suggest hemolysis, and support for this comes from a low haptoglobin, and a raised indirect bilirubin, as well as a high LDH. The positive Direct Coombs' test indicates that this is an autoimmune process.

Physical examination is consistent with CLL.

One of the characteristic, and common complications of CLL is a warm autoimmune hemolytic anemia. Autoimmune thrombocytopenia also occurs, but can only be diagnosed by looking at the number of megakaryocytes in the bone marrow. Where there is autoimmune destruction of platelets, there will be an increase in bone marrow megakaryocytes, but where marrow failure is the cause of the thrombocytopenia, the number of megakaryocytes in the bone marrow will be decreased.

Diagnosis: 1. chronic lymphocytic leukemia

2. warm autoimmune hemolytic anemia

3. autoimmune thrombocytopenia

Case 12: Here is a macrocytic anemia, and a mild pancytopenia. Vitamin B₁₂ or folate deficiency or ethanol have to be considered, but there is nothing in the history to suggest these, and the levels of vitamin B₁₂ and folate are normal.

More importantly, there are "rouleaux" (stacked red blood cells) on the blood film report, and again a leukoerythroblastic blood picture. Rouleaux indicate a high serum protein concentration, and occur in many diseases. They are particularly prominent in those diseases which cause a very high erythrocyte sedimentation rate (ESR), such as multiple myeloma, cancers. chronic infections (eg TB), and connective tissue diseases.

Here, the history of back pain would be consistent with vertebral collapse, and the finding of rouleaux together with the leukoerythroblastic picture would be consistent with the presence of a bone marrow neoplastic disorder, such as multiple myeloma, or secondary cancer (eg lung, breast). A bone marrow is necessary, and studies of the serum and urine proteins, and since a paraprotein is discovered, also a skeletal survey.

Diagnosis: multiple myeloma