Haem Flashcards
Outline acute myeloid leukaemia (AML).
• Adults 40-60y common. • Neoplastic blasts in BM, blood, liver, spleen. • Commonest is M3. • Anaemia, fever, bleeding. • Hepatosplenomegaly* moderate (leukaemic infiltration). • No significant lymphadenopathy (can be there but not significant). • Gum hypertrophy* (leukaemic infiltration). • Increased infections - candidiasis (oral thrush - fungal), chronic infections also common (decreased WBC). • Gingivitis and hyperplasia. • Bruising - purpura (decrease platelets). Microscopy: • Plenty of large round blast cells with more clear cytoplasm with granules and Auer rods - myeloblasts. • The same large blast cells but have more clear cytoplasm with plenty of granules. The granules may join to form crystal like structures within the cytoplasm known as Auer rods. • Myeloblasts have fine lacy chromatin, many nucleoli, more cytoplasm, cytoplasmic granules.
Differentiate between ALL and AML.
ALL: • Children, lymphadenopathy. • Scanty cytoplasm. • No granules. AML: • Adults, hepatomegaly. • More cytoplasm. • Granules + Auer Rods. • Both have anaemia, fever, infections and bleeding as common features. • Both leukaemias can occur at any age.
Outline chronic myeloid leukaemia (CML).
• Middle age 40-60y. • Philadelphia chromosome, t(9:22) - characterised by the Philadelphia chromosome - short 22 chromosome where it has lost a portion of its segment of chromosome to chromosome 9 (translocation). • BCR-ABL fusion gene - oncogene. - Activation of BCR-ABL fusion gene - oncogene → produces carcinogenesis - uncontrolled proliferation of blast cells. These blast cells mature into different forms of WBC - there will be basophils, eosinophils and neutrophils (more common) - mature cells of all types. • Anaemia, fever and bleeding. • Marked leucocytosis - >50 (DDx: leukaemoid reaction). Marked left shift. • Marked hepatosplenomegaly. • Clinical phases: - Chronic - slow progress - years (commonest) - gradually develop weakness, fatigue, anaemia, infections, bleeding. - Accelerated - rapid progress - months - rapid progression usually within months, blast cells increase. - Blast crisis - acute leukaemia - weeks - all the blasts take over the space. No more mature cells (very few mature cells). Patients deteriorates within a week - very serious clinical condition like acute leukaemia - blast crisis of CML. Microscopy: • Marked increased in WBCs, marked shift to the left (very immature cells) with basophils. • Increased numbers maturing myeloid cells (neutrophils, myelocytes, eosinophils, basophils) - increased progenitor cells but blasts make up less than 10% circulatory cells.
Outline multiple myeloma.
Malignant plasma cells secrete monoclonal Ab (‘M protein’ or ‘paraprotein’)
May be heavy chain + light chain OR light chain only
Heavy chain - IgG 50%, IgA 20%, others rare
Light chain - kappa or lambda with abnormal kappa:lamda ratio
Urine has Bence-Jones protein which are found in myeloma in renal impairment induced by hypercalcemia or from proteins themselves (monoclonal light chains in urine)
Clinical features;
CRAB (main features) - hypercalcaemia, renal impairment, anemia, bony lytic lesions
Bone disease
Sx
Bone pain & tenderness (main symptom)
Usually back pain & pathological #s
X-ray
Lytic lesions of skull, spine, ribs & proximal long bones
Anemia
Secondary to BM suppression
Weakness, fatigue, pallor, SOB, headaches, palpitations
Hypercalcaemia
Secondary to ↑bone turnover
Features
Abdo groans - abdominal pain (constipation, pancreatitis, stones), PROFOUND constipation, N&V
Psychic moans - lethargy, confusion, delirium, psychosis, depression, memory loss
Renal stones (also gallstones?)
Thrones - constipation + nephrogenic DI (polyuria, polydipsia)
Painful bones
Muscular - weakness, hyporeflexia
Renal failure
Secondary to any of
Myeloma kidney - light chain cast nephropathy (casts of Ig plug tubules causing renal failure)
Hypercalcaemia - dehydration (polyuria), renal stones, tubular damage from calcium deposition
Infection
Others
Neurological deficits - vertebral # & extramedullary plasmacytomas of vertebrae
Bleeding - secondary to thrombocytopenia
Extramedullary plasmacytoma - soft tissue mass of plasma cells (may cause cord compression)
Hyperviscosity - thromboembolism (stroke, angina, MI), headaches, visual symptoms
Amyloidosis - infiltration of proteins in tissues can affect multiple systems including cardiac (arrhythmias, HF), neuro (carpal tunnel etc.)
Differentiate between Hodgkin’s lymphoma and Non-Hodgkin’s lymphoma.
Hodgkin’s Lymphoma: • Age - average age 28y with 2 peaks - 25y and 65y. • Occurrence - <10% of all lymphomas. • Location and spread - cervical, chest and mediastinal 85%, extranodal in 4% Contiguous spread. Mesenteric & Waldeyer ring involvement - uncommon. • Affected cells - B lymphocytes with RS cells. • Symptoms - more likely to have systemic B symptoms. • Progression - early diagnosis, predictable, better prognosis. Ann arbour staging system
-Mx; combination chemo and radiotherapy
Non-Hodgkin’s lymphoma: • Age - average age is about 67y. • Occurrence - >60% of all lymphomas. • Location and spread - multiple sites. Chest in 40%, extra nodal in ~23% and BM non-contiguous spread. Mesenteric & Waldeyer ring (tonsilar ring) involvement common. • Affected cells - B, T, histiocytes, NK cells depending on the subtype. No RS cells. • Symptoms - less likely to have B symptoms (27%). • Progression - less predictable, early spread, good to worse prognosis.
-Mx; combination chemo
Outline polycythemia rubra vera.
• Excess proliferation of all cells. Increased RBC mass. - Disease due to marked proliferation in the marrow of erythroid cells - hypercellular marrow - too many RBCs. - Increased RBC and increased HCT. Also associated with increased WBC, increased platelets (MPD - excess proliferation of all cells, dominantly effecting RBC). • Activation of JAK2 - in all cases. JAK2 (common in all MPD) → tyrosine kinase activator → makes the neoplastic cells growth factor independent proliferation - do not require EPO - start continuously dividing and producing RBC. • Neoplastic - growth factor independent proliferation. • Low serum erythropoietin - serum EPO decreased as there is increased RBC (suppressed). • High viscosity, vascular stasis, infarctions. - Neoplastic erythrocytes → plenty of RBCs → blood becomes thick (too many RBCs) - vascular stasis and infarction. - Blocking/rupture of capillaries also common. • Bleeding - BV damage, platelet abnormality. • Hypercellular bone marrow - plenty of erythroid cells. • May progress to myelofibrosis after many years. Rarely to AML.
Outline essential thrombocythemia
• JAK2 tyrosine kinase activation. • Increased platelets, megakaryocytes. - Same mutation is effecting megakaryocytes → increased production of platelets (cancerous stem cells are producing uncontrolled continuous proliferation of abnormal platelets - do not function (haemostasis) → cause bleeding. • Large and abnormal platelets → bleeding (patients present with marked bleeding). • Primary myelofibrosis common - PDGF. - Increased platelets produce PDGF (platelet derived growth factor) - stimulates fibroblasts (same as wound healing) → results in scarring of the marrow. • Hepatosplenomegaly (neoplastic stem cells infiltrate into the liver, spleen and lymph nodes). • Transformation to AML - late and rare (may progress to AML at later stage). • Clinically see plenty of platelets (high platelet counts), even megakaryocytes come out into the peripheral blood (normally should only be in the marrow). The platelets are very large - all products of malignant megakaryocytes.
Outline primary myelofibrosis.
-Ix involved
- Abnormal megakaryocyte–> these release PDGF and transforming GF–> stimulate fibrosis in the BM–> scarred BM causes haematopoietic stem cells to move to liver/spleen and undergo extramedullary haematopoiesis
- Causes massive splenomegaly and hepatomegaly
IX;
BM aspirate (dense reticulin fibres, fiborsis and osteosclerosis)
-X-ray; bone sclerosis
-blood smear; anaemia, tear drop cells
-cytogenics–> JAK-2
What are the 4 main causes of anaemia?
-Failure of erythrocyte production. • Loss of erythrocytes. • Abnormality of erythrocytes. • Destruction of erythrocytes.
Identify the clinical features of megaloblastic anaemia.
• May be asymptomatic (detected by increased MCV on routine blood count). • Symptoms of anaemia. • GIT symptoms - anorexia, weight loss, diarrhoea or constipation, glossitis, chelitis, mild jaundice (unconjugated - due to haemolysis). • Skin pigmentation (pallor/jaundice). • Bruising/mucosal haemorrhage and susceptibility to infections (particularly of the respiratory and urinary tract) - thrombocytopenia and leukopenia may occur. • Lesions of nervous system due to vitamin B12 deficiency. - Brain: lesions in the white matter → dementia. - Peripheral nerves: degeneration of myelin sheaths. - Spinal cord: lesions of corticospinal tracts and posterior columns. • Mild fever in severely anaemic patients. • Infertility in both men and women.
Outline the investigations for megaloblastic anaemia.
FBC: • Hb decreased, MCV increased. • RBC count decreased. • MCH high, MCHC normal - total Hb per RBC is high but the percentage of space occupied by Hb is the same (concentration is the same). • WBCs, platelets decreased. • S-vitamin B12 level. • S-folate level, RBC folate. • Iron studies as a mixed deficiency may be present. Antibodies: • Intrinsic factor antibody - Type I - blocking - Ab prevents the combination of IF and vitamin B12. - Type II - binding - Ab prevents the attachment of IF to ileal mucosa. • Parietal cell antibody. Evidence for haemolysis: • Urine - increased urobilinogen, haemosiderinuria. • Blood - increased unconjugated bilirubin, decreased haptoglobin level, increased lactate dehydrogenase (LDH).
Describe the morphology/clinical features of DIC.
• Extensive thrombosis. • Severe bleeding. • Shock. • Renal/organ failure.
Outline the laboratory diagnosis of DIC.
• Decreased coagulation factors and platelets - all tests abnormal* (everything gets used up - DIC is life-threatening - extensive severe bleeding both superficial and deep). • Increased fibrin degradation products (FDP and D-dimer) - extensive breakdown of thrombi, both FDP and D-dimer (also breakdown product of fibrin) raised. • Release of tissue factor → widespread microvascular thrombosis → leading to ischaemic tissue damage and consumption of clotting factors and platelets → ultimately leading to extensive bleeding and also fibrinolysis. • All this leads to decreased platelets, increased PT, PTT, TT and increased FDP and D-dimer.
Differentiate between DIC, TTP and HUS (systemic activation of haemostasis).
• DIC - more common, activation of both platelets and coagulation. • TTP - activation of only platelets with the neurological deficits. • HUS - activation of only platelets with renal failure.
