A 26-year-old previously well woman on no medication presents with the recent-onset of easy bruising. She has two small oral mucosal haemorrhages, scattered bruises and petechiae around the ankles but no other abnormalities on examination. Human immunodeficiency virus (HIV) antibody test is negative. The full blood count shows:
Prothrombin time-international normalised ratio (PT-INR) and activated partial thromboplastin time (APTT) are normal and bone marrow examination is also normal except for an increase in megakaryocytes. The most appropriate initial therapy is: A. intravenous gamma globulin. B. oral tranexamic acid. C. platelet transfusion. D. oral prednis(ol)one. E. oral danazol.
A 23-year-old woman presents with several days history of petechiae of the skin and oral mucosa. There is no history of infection or medication apart from the oral contraceptive pill. The patient is well and examination is unremarkable except for the petechiae. Investigations reveal:
Which one of the following is the most appropriate treatment? A. Oral prednis(ol)one. B. Intravenous immunoglobulin. C. Platelet transfusion. D. Danazol. E. Splenectomy.
What is the cause of red cell aplasia?
What are the characteristics of the anaemia?
What is the treatment?
Idiopathic and autoimmune (mediated by T-lymphocytes or IgG antibody to erythroid precursors. Viral: (parvo, herpes, HIV and hepatitis)ThymomaOther malignancy
Drugs: EPO (alpha aka Eprex), MMF
Severe and normochromic with absent retics
BMBx: All non- erythroid elements are present and normal, but erythroid precursors are markedly reduced or absent. In some cases, chest imaging studies will reveal a thymoma.
Combination of antithymocyte globulin and a calcineurin inhibitor (cyclosporine or tacrolimus)—similar to therapy of aplastic anemia.
Drugs: EPO (alpha aka Eprex), MMF
What is the mechanism of EPO related red-cell aplasia?
Neutralising antibodies, and will cross-react with all currently available erythropoietic agents (epoetin alfa and beta, and darbepoetin alfa), in addition to endogenous EPO.
In which conditions are spherocytes found?
Spherocytes are found in hereditary spherocytosis and autoimmune hemolytic anemia.
What is a ringed sideroblast?
Ring sideroblasts are named so because of the arrangement of the iron granules in a ring form in mitochondria around the nucleus of an erythroid precursor
The body has iron available but cannot incorporate it into hemoglobin, which red blood cells need to transport oxygen efficiently.
What are the diagnostic essentials of myelodysplastic syndrome?
- cytopaenia with hyper cellular BM (but not more than 20% blasts otherwise it's AML)- morphologic abnormalities in two or more cell lines
What are the causes of myelodysplastic syndrome?
Idiopathic / cytotoxic CTx, RTx or bothBenzene
Red cell aplasia and Fanconi's anaemia can transform to MDS
What is the classification of stages of MDS?
Refractory anaemia - no excess bone marrow blasts, may or may not have ringed sideroblasts
Refractory anaemia w/ excess blasts
Chronic myelomonocytic leukaemia - MDS + peripheral blood monocytosis
Prognosis worsens with each.
What is 5q- syndrome?
Myelodysplasia with:5q- syndrome (indolent disease)Refractory anaemia with loss of long arm of chromosome 5Good prognosis
How is the severity and survival of myelodysplasia ranked?
IPSS - survival and rate of progression AMLSurvival related to:Percentage of bone marrow blasts 0-10% mild, 21-30% is poorKaryotype: Normal, Y-, 5q-, 20q- = goodBad: Cr 7 (monosomy 7), or if there are 3 or more abnormalitiesCytopaenias - None or 1 cell line is good, 2 or 3 is bad.
What are the clinical findings in MDS?
Clinical findingsAge >60Incidental finding or fatigue/infection/bleeding due to bone marrow failureFever, weight loss, general debilitySplenomegaly, pallor and bleeding
What are the lab findings in myelodysplasia?
Marked anaemia w/ normal or elevated MCVLow WCC and neutropeniaSmear: Macro-ovalocytes, bilobed neutrophils (Pelger Huet abnormality), myeloid left shift with small numbers promyelocaytes or blasts, normal or reduced hypo granular plateletsBMBx: Erythroid hyperplasia, megaloblastosis: nuclear budding, multinucleate erythroid precursorsLeft shifted myeloid series, characteristic: dwarf megakaryocytic with a unloved nucleusPrussian blue stain: ringed sideroblasts
How do you differentiate myelodysplasia from MDS?
AML: MDS has <20% blasts, AML has >20%
What is the treatment of myelodysplasia?
EPO if anaemic if EPO levels are lowG-CSF may help response to EPO.Highest transfusion requirements = least likely to respondLenalidomide for transfusion dependent anaemia due to MDS esp for 5q- syndrome (less success w/o it). SEs: neutropenia, thrombocytopaenia, VTE - must use aspirin prophylaxis. Not useful for other cell lines.Iron chelation if transfusion dependent.High risk - azacitidine
What is the prognosis of myelodysplasia
Ultimately fatal, cure rates of 30-60%5q- 5 year survival over 90% or low risk diseaseExcess blasts or CMML = higher chance of AML and short survival w/o Allo SCT.
What are the diagnostic essentials of hairy cell leukaemia?
Pancytopenia.Splenomegaly, often massive.Hairy cells present on blood smear and especially in bone marrow biopsy
What is hairy cell leukaemia?
Rare mature b-lymphocytosis with hairy cytoplasmic projections.
What are the signs and symptoms of hairy cell leukaemia?
Middle aged men, 55 years 5:1 M:FFatigueSx related to markedly enlarged spleenRecurrent infection inc mycobacterial infectionsHepatomegaly in 50%No lymphadenopathy
What are the lab findings in hairy cell leukaemia?
Pancytopaenia (hallmark)Anaemia (universal), thombocytopaenia and neutropeniaSmear: ‘hairy cells’ B-lymphocytes with cytoplasmic projectionsBMBx: dry tapSplenic infiltrate of red pulp with hair cells (lymphoma it’s the white pulp)Immunophenotyping: CD11c, CD20, Cd22, CD25, CD103, and CD123
What is the treatment of hairy cell leukaemia?
IFN-aCladribine (purine analogue)Pentostatin
What is the prognosis of hairy cell leukaemia?
Good - >95% of patients are alive longer than 10 yearsIf secondary to CLL - worse prog
What are the diagnostic essentials of Waldenstrom's macroglobulinaemia?
Monoclonal IgM paraproteinBM infiltration by plasmacytic lymphocytesAbsence of lytic bone disease
What is Waldenstrom's macroglobulinaemia?
IgM hypergammaglobulinaemia in setting of NHL.B-lymphocytes that are a morphological hybrid of lymphocytes and plasma cells.Cells secrete IgM paraprotein.
What are the clinical findings of Waldenstrom's macroglobulinaemia?
Insidious onset in 60s-70sFatigue related to anaemiaHyperviscosity --> mucosal and GI bleeding, retinal vein engorgement due to engorged blood vessels and platelet dysfunction--> neuro sx, nausea, vertigo, visual changes, stupor, coma--> cold agglutinin disease (haemolysis), chronic demyelinating peripheral neuropathy
HepatosplenomegalyPurpuraNo bone tendernessNo renal diseaseNo lytic lesions
What are the lab findings in Waldenstrom's macroglobulinaemia?
Anaemia, roleaux, RBC agglutination at rom tempAnaemia is secondary to expansion of plasma volume (by 50-100%Plasmacytic lymphocytes on smearBMBx: Infiltration of plasmacytic lymphocytesHallmark: Monoclonal IgM spike on serum PeP in the B-globulin regionHigh serum viscosity (symptoms develop at 4x water viscosity, severe at 6xPositive Coombs for complementCold agglutinin or cryoglobulin properties
Why and how should you repeat protein electrophoresis if a suspected test for Waldenstrom's macroglobulinaemia comes back with hypogammaglobulinaemia?
Temp must be maintained at body temp of 37c or the paraprotein may precipitate out. Sample should recollected and kept warm.
What is the differential dx of Waldenstrom's macroglobulinaemia?
MGUS --> W has monoclonal malignant cellsCLL --> Absence of CD5, different morphology, absence of lymphocytosisMultiple myeloma --> BM morphology, IgM paraprotein, absence of bone and renal disease
What is the treatment of Waldenstrom's macroglobulinaemia?
Hyperviscosity syndrome (stupor, coma, pulm oedema) --> emergency --> plasmapheresisOtherwisePeriodic plasmapheresisFCR (Fludarabine, cyclophosphamide, rituximab)
What treatment does all indolant malignant lymphoid diseases have in common?
Rituximab (anti-CD20 antibody)