formative Flashcards
A 28 year old woman attending the antenatal clinic has a blood count performed with the results as follows: Haemoglobin 82g/L, MCV 87 fl, white cell count 6.4 x 109/l, neutrophil count 3.8 x 109/l and platelet count 270 x 109/l. Haemoglobin analysis identifies a high level of Hb S without detectable HbA.
sickle cell anaemia
The detection of HbS (glutamic acid to valine substitution in the beta chain of haemoglobin) indicates that the patient has sickle cell anaemia (homozygous)
(HbS would also have been detected if the patient had sickle trait (heterozygous), but HbA would also have been present. Also, the patient would not be expected to be anaemic on account of sickle trait.)
A 28 year old man has a blood count performed with the results as follows: Haemoglobin 152g/L, MCV 65 fl, white cell count 6.4 x 109/l, neutrophil count 3.8 x 109/l and platelet count 270 x 109/l. Haemoglobin analysis identifies the presence of raised Hb A2.
beta thalassaemia trait
The disproportionate reduction in MCV relative to the haemoglobin reflects a haemoglobinopathy trait (heterozygous state) which accompanied by an increase in HbA2 (α2δ2).
An 18 year old man with fatigue and a family history of a haemolytic disorder has a blood count performed with the results as follows: Haemoglobin 82g/L, MCV 94 fl, white cell count 5.9 x 109/l, neutrophil count 3.2 x 109/l and platelet count 170 x 109/l. Blood film shows polychromasia and red cells with loss of central pallor.
hereditary spherocytosis
Red cells that have lost central pallor are called spherocytes, and an excess of these in a patient with family history of haemolytic anaemia makes hereditary spherocytosis the likely diagnosis.
mechanisn of action of clopidogrel
it is an ADP antagonist
clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. This action is irreversible.
mechanism of action of aspirin
it irreversibly inactivates cyclooxygenase 1
This irreversibly stops production of thromboxane which is an important initiator of platelet aggregation.
mechanism of action of rivaroxiban
highly selective direct inhibitor of activated factor X
Riveroxiban competitively inhibits factor Xa. Factor Xa along with factor Va for the prothrombinase complex which converts prothrombin to thrombin
A 68 year old woman with fatigue has a blood count performed and the results are as follows: Haemoglobin 87g/L, MCV 110 fl, white cell count 2.4 x 109/l, neutrophil count 1 x 109/l and platelet count 100 x 109/l. The blood film shows macroovalocytes and hypersegmented neutrophils.
pernicious anaemia
Pernicious anaemia that causes B12 deficiency will result in impaired nuclear maturation affecting the development of all three haemopoietic lineages, so pancytopenia with macrocytic red cell development can occur in deficiency states.
–>Paradoxically some patients can present with neuropathy related to B12 deficiency and have apparently normal blood counts.
A 58 year old man with fatigue has a blood count performed and the results are as follows: Haemoglobin 77g/L, MCV 90 fl, white cell count 22.4 x 109/l, neutrophil count 0.1 x 109/l and platelet count 30 x 109/l. The blood film shows an excess of blasts with Auer rods.
acute myeloid leukaemia
Marrow failure (resulting in the low Hb, Neutrophil and Platelet count) in acute myeloid leukaemia is caused due to the excessive proliferation of primitive cells (myeloblasts). Abnormalities of granulation in these blasts can be visualised in the form of Auer rods.
A 52 year old man with a stroke has a blood count performed and the results are as follows: Haemoglobin 140g/L, MCV 90 fl, white cell count 10.4 x 109/l, neutrophil count 6.8 x 109/l and platelet count 930 x 109/l. The blood film shows an excess of platelets with some giant forms.
essential thrombocythaemia
–>a chronic myeloproliferative disorder characterised by excess production of platelets in the bone marrow and an increased risk of thrombosis.
Temperature 37.8C pulse 90 bpm, two hours after starting a blood transfusion. Otherwise well with normal blood pressure.
febrile non-haemolytic transfusion reaction
–>Fever but no hemolysis. It is most commonly caused by antibodies directed against donor leukocytes and HLA antigens present in the patient or donor cytokines present in the transfusion that were released by white cells in the blood that have broken down during storage.
92 year old woman who is breathless after receiving a 4 unit red cell transfusion for chronic anaemia.
transfusion associated circulatory overload
->TACO can occur when patients with chronic anaemia and a compensatory high cardiac output are given a large volume load. The result is often pulmonary oedema.
48 year old man becoming breathlessness two hours after an infusion of fresh frozen plasma.
transfusion related acute lung injury
TRALI is caused by anti- leucocyte antibodies present in the donation that bind to the patients white cells and cause acute lung injury by degranulation of the affected neutrophils in the lungs. Pulmonary infiltrates are seen on CXR.
A 77 year old asymptomatic man is found to have a lymphocytosis.
chronic lymphocytic leukaemia
-> that is a clonal (neoplastic) disorder of B cells. Many patients will have asymptomatic disease.
causes of hereditary thrombophilia
factor V leiden
antithrombin deficiency
protein C deficienct
protein S deficiency
(antiphospholipid syndrome is ACQUIRED)
mechanism of sickle cell disease
point mutation in globin gene
->caused by a point mutation in the beta chain and this predisposes the haemoglobin to polymerisation resulting in sickled cells and reduced red cell survival.
mechanism of myelodysplasia
acquired DNA mutations in haematopoietic stem cells
-> Myelodysplasia is a stem cell malignancy that results in ineffective haematopoiesis. It can progress to AML.
mechanism of hereditary spherocytosis
Congenital mutation in structural red cell proteins
-> A mutation in one of the structural red cell membrane proteins resulting in reduced red cell deformability and so membrane is removed in spleen (resulting in spherocytes) and reduced red cell survival
A 28 year old woman attending the antenatal clinic has a blood count performed with the results as follows: Haemoglobin 112g/L, MCV 65 fl, MCH 20 pg, white cell count 6.4 x 109/l, neutrophil count 3.8 x 109/l and platelet count 170 x 109/l. The serum ferritin is within the normal range.
what test is likely to be diagnostic?
haemoglobin analysis by high performace liquid chromatography (HPLC)
->The mild anaemia in the presence of a normal serum ferritin reflects the dilutional (physiological) anaemia of pregnancy. The normal serum ferritin makes iron deficiency unlikely. The disproportionate reduction in MCV and MCH compared to the haemoglobin indicates the possibility of a haemoglobinopathy trait (heterozygous) which is best investigated by haemoglobin analysis.
A 52 year-old asymptomatic, fit man with no significant medical history has a blood count performed with the results as follows: Haemoglobin 200g/L, MCV 81 fl, white cell count 11 x 109/l, neutrophil count 7.2 x 109/l and platelet count 402 x 109/l. Blood film confirms the blood count abnormalities.
which test is likely to be diagnostic?
JAK2
A high haemoglobin in someone without a history to suggest a secondary polycythaemia should be investigated by the analysis of the JAK2 gene, which has a somatic mutation in up to 95-97% of patients with myeloproliferative polycythaemia (also called polycythaemia rubra vera or primary polycythaemia).
A 21 year-old man with fatigue and easy bruising has a blood count performed with the results as follows: Haemoglobin 8.0g/L, MCV 92 fl, white cell count 50 x 109/l, neutrophil count 0.2 x 109/l and platelet count 40 x 109/l. The blood film shows an excess of blasts.
which test is likely diagnostic?
immunophenotyping by flow-cytometry
The cytopenias and excess of blasts are highly suggestive of an acute leukaemia. Immunophenotyping will clarify the lineage involved (ie myeloid or lymphoid) which is important therapeutically.
Uncontrolled production of essentially normally functioning blood cells
polycythaemia rubra vera
-> The red cells production is uncontrolled (unlike secondary polychythaemia where it is controlled by high epo driven by the secondary cause eg hypoxia). The result is an excess of normally functioning red cells. In CLL cells have no useful function.
Uncontrolled production of immature blood cells in the bone marrow
acute myeloid leukaemia
-> AML is a bone marrow based malignancy where there is a block in differentiation and an excess of primitive cells accumulate rapidly.
Clonal B cell disorder usually resulting in a large number of circulating malignant cells
chronic lymphocytic leukaemia
->CLL is a chronic leukaemia so unlike acute leukaemia there is not a block on early differentiation but failure of cell death and so a steady accumulation of cells over time. They are produced in bone marrow and seen circulating as an excess of small mature lymphocytes in the blood (often with smear cells seen on a blood film). Diagnosis is confirmed by peripheral blood immunophenotyping.
thrombophilia
an increased thrombotic tendency
