Haemotolgy Flashcards

Question

Sideroblastic anemia

Answer 1

where red cells fail to completely form heme, whose biosynthesis takes place partly in the mitochondrion. This leads to deposits of iron in the mitochondria that form a ring around the nucleus called a ring sideroblast. It may be congenital or acquired

Answer 2

Congenital cause: * Delta-aminolevulinate synthase-2 deficiency Acquired causes * Myelodysplasia * Alcohol * Lead * Chloramphenicol and Anti-TB medications (INH + Pyrazinamide)

Answer 3

Investigations * Hypochromic microcytic anemia (more so in congenital) * Bone marrow: sideroblasts and ↑ iron stores Management * Supportive * Treat any underlying cause * Pyridoxine may help

Answer 4

diagnosed when there is unexplained anaemia and reticulocytopenia, with a complete absence of red cell precursors in the bone marrow, but with preservation of other cell lines.

Answer 5

* Either spontaneously or associated with * Thymoma * Autoimmune * Lymphoproliferative disorder

Answer 6

commonest red cell enzyme defect. It is more common in people from the Mediterranean and Africa and is inherited in an X-linked recessive fashion. Many drugs can precipitate a crisis as well as infections and broad (fava) beans

Answer 7

Features * Neonatal jaundice is often seen * Intravascular hemolysis * Heinz bodies on blood films

Answer 8

rugs causing hemolysis * Anti-malarials: primaquine * Ciprofloxacin * Sulfonamides * Co-trimoxazole (because it contains sulfa)

Answer 9

is an acquired disorder leading to hemolysis (mainly intravascular) of hematological cells. It is thought to be caused by ↑ sensitivity of cell membranes to complement (see below) due to a lack of glycoprotein glycosyl-phosphatidylinositol (GPI). Patients are more prone to venous thrombosis

Answer 10

* GPI can be thought of as an anchor which attaches surface proteins to the cell membrane * Complement-regulating surface proteins, e.g. decay-accelerating factor (DAF), are not properly bound to the cell membrane due a lack of GPI * Thrombosis is thought to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation

Answer 11

Diagnosis * Flow cytometry of blood to detect low levels of CD59 and CD55 has now replaced Ham's test as the gold standard investigation in PNH * Ham's test: acid-induced hemolysis (normal red cells would not) Management * Blood product replacement * Anticoagulation * Eculizumab, a monoclonal antibody directed against terminal protein C5, is currently being trialled and is showing promise in reducing intravascular hemolysis * Stem cell transplantation

Answer 12

Relative causes * Dehydration * Stress: Gaisbock syndrome Primauy * Polycythaemia Rubra Vera 2ndary COPD * Altitude * Obstructive sleep apnoea * Excessive erythropoietin: cerebellar hemangioma, hypernephroma, hepatoma, uterine fibroids*

Answer 13

Myeloproliferative disorder c aused by clonal proliferation of a marrow stem cell leading to ↑ RBCs, often accompanied by ↑ WBC (neutrophils) and ↑ platelets. mutation in JAK2 is present in approximately 95% of patients with PRV

Answer 14

Features * Hyperviscosity (headaches, tinnitus, visual disturbance, cyanosis, joint pain) * Pruritus, typically after a hot bath * Splenomegaly ± Hepatomegaly * Hemorrhage (secondary to abnormal platelet function not number) * Plethoric appearance * Low ESR * Hypertension in a third of patients

Answer 15

* ↑ Hemoglobin and hematocrit * ↑ Leucocyte alkaline phosphatase (LAP) * Additional: o ±↑WBCand↑PLT o ±↑Plasmavolume o ↑ Vitamin B12 o ↑ Red cell mass o ↓ Erythropoietin level

Answer 16

Management * Venesection - first line treatment * Hydroxyurea -slight ↑ risk of secondary leukemia * Allopurinol & Phosphorus-32 therapy Prognosis * Thrombotic events are a significant cause of morbidity and mortality * 30% of patients progress to myelofibrosis * 5-15% of patients progress to acute leukemia

Answer 17

A1 High hematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted) A2 Mutation in JAK2

Answer 18

diagnosis requires A1 + A2 + A3 + either another A or two B criteria A1 Raised red cell mass (>25% above predicted) OR hematocrit >0.60 in men, >0.56 in women A2 Absence of mutation in JAK2 A3 No cause of secondary erythrocytosis A4 Palpable splenomegaly A5 Presence of an acquired genetic abnormality (excluding BCR-ABL) in the hematopoietic cells B1 Thrombocytosis (platelet count >450 * 109/l) B2 Neutrophil leucocytosis (neutrophil count > 10 * 109/l in non-smokers; > 12.5*109/l in smokers) B3 Radiological evidence of splenomegaly B4 Endogenous erythroid colonies or low serum erythropoietin

Answer 19

Neutropenia is defined as an absolute peripheral blood neutrophil count of <2.0 × 10*9/l. There is a racial variation: black and Middle Eastern people may have neutrophil counts of <1.5 × 10*9/l normally.

Answer 20

Congenital neutropenia: * Kostmann’s syndrome * Chediak–Higashi * Schwachmann–Diamond syndrome * Cyclical neutropenia Acquired neutropenia: * Infection: viral e.g. influenza, HIV, hepatitis, bacterial sepsis. * Drugs: anticonvulsants (phenytoin) – anti-thyroid (carbimazole) – phenothiazines (chlorpromazine) – antibacterial agents (cotrimoxazole) – ACE-inhibitors (ramipril) * Immune-mediated: SLE, Felty’s syndrome (Rheumatoid Arthritis + Neutropenia + Splenomegaly) * Bone marrow failure: leukaemia, lymphoma, Hematinic deficiency * Splenomegaly: any cause

Answer 21

Investigations: * Blood film * Hematinics: factors that ↑Hb (Iron, TIBC, Vit B12, Folic Acid, Vit D) * Autoimmune profile bone marrow aspirate/trephine are indicated if there are severe or prolonged neutropenia or features suggestive of marrow failure

Answer 22

* High leukocyte alkaline phosphatase score * Toxic granulation (Dohle bodies) in the white cells * 'Left shift' of neutrophils i.e. ↑neutrophils or ≤ 3 segments of the nucleus

Answer 23

Thought to be caused by hyperplasia of abnormal megakaryocytes [bone marrow cell responsible for the production of blood thrombocytes (platelets)] * The resultant release of platelet derived growth factor is thought to stimulate fibroblasts * Hematopoiesis develops in the liver and spleen

Answer 24

Features * E.g. Elderly person with symptoms of anemia e.g. Fatigue (the most common presenting symptom) * Massive splenomegaly * Hypermetabolic symptoms: weight loss, night sweats etc

Answer 25

Laboratory findings * Anemia * High WBC and platelet count early in the disease * 'Tear-drop' poikilocytes on blood film * Unobtainable bone marrow biopsy - 'dry tap' therefore trephine biopsy needed * High urate and LDH (reflect ↑ cell turnover)

Answer 26

Presentation: * Anaemia } * Infection * Bleeding Due to pancytopenia

Answer 27

investigations: * Serial blood counts show evidence of increasing bone marrow failure * Bone marrow shows increased cellularity. Management: * < 5% blasts in the bone marrow → manage conservatively. * ↑ WBC → gentle chemotherapy. * < 60 years old → Intensive chemotherapy

Answer 28

The Philadelphia chromosome is present in more than 95% of patients with CML . It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34:q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal

Answer 29

Presentation (40-50 years) * Middle-age * Anemia, weight loss * Splenomegaly may be marked (lethargy, anorexia, abdominal discomfort – 75% palpable spleen) * Hepatomegaly and lymphadenopathy are uncommon * Spectrum of myeloid cells seen in peripheral blood * ↓ neutrophil alkaline phosphatase * May undergo blast transformation (AML in 80%, ALL in 20%)

Answer 30

Diagnosis: * Philadelphia is confirmatory * Peripheral blood film: (leukocytosis in all stages of differentiation within the myeloid linage) The Only MRCP Notes You’ll Ever Need 142 / 546 www.sudamedica.com * Basophilia is important diagnostic marker especially when Philadelphia is absent * Monocytopenia * Bone-marrow hypercellularity with ↑ myloid-erythroid ratio

Answer 31

Management * Hydroxyurea (also used in PRV, painful attacks in sicklers and as antiretroviral in HIV) * Interferon- α * Imatinib (inhibitor of tyrosine kinase) * Allogenic bone marrow transplant (optimum management)

Answer 32

s the most common form of acute leukemia in adults. It may occur as a primary disease or following a secondary transformation of a myeloproliferative disorder (e.g CML, myelofibrosis). > 30% blasts are almost diagnostic of AML.

Answer 33

Presentation: * Early signs are vague and non-specific (influenza-like) * Persistent or frequent infections (due to ↓ WBC) * Bruising and petechiae (due to ↓ PLT) * Splenomegaly may occur but typically mild and asymptomatic. Lymph node swelling is rare.

Answer 34

hemotherapy: divided into two phases: 1. Induction: All types except M3 are given induction with cytarabine (ara-C) and an anthracycline (such as daunorubicin or idarubicin).This regimen is known as "7+3", because the ara-C is given as a continuous IVI for 7 days while the anthracycline is given for 3 consecutive days as an IV push. 2. Consolidation: even after complete remission, very few leukemic cells likely to remain undetected with current diagnostic techniques. If no further post-remission therapy is given, almost all patients will eventually relapse. Therefore, more therapy is necessary to eliminate non-detectable disease and prevent relapse — that is, to achieve a cure. The specific type of postremission therapy is individualized based on prognostic factors and general health: 􏱎 For good-prognosis leukemias [t(8;21), and t(15;17)], patients will typically undergo an additional 3–5 courses of intensive chemotherapy 􏱎 For patients at high risk of relapse (e.g. those with high-risk cytogenetics, underlying MDS, or therapy-related AML), allogeneic stem cell transplantation is usually recommended

Answer 35

MO - Undifferentiated * M1 - Without maturation * M2 - With granulocytic maturation * M3 - Acute promyelocytic * M4 - Granulocytic and monocytic maturation * M5 - Monocytic * M6 - Erythroleukemia * M7 – Megakaryoblastic

Answer 36

> 60 years * > 20% blasts after first course of chemo * Cytogenics: deletions of chromosome 5 or 7

Answer 37

Associated with t(15:17) * Fusion of PML and RAR-α genes * Presents younger than other types of AML (average = 25 years old) * * Good prognosis (curable with well-documented treatment protocols) * Treated with the ATRA in addition to induction chemotherapy. Care must be taken to prevent DIC, complicating the treatment of APL when the promyelocytes release the contents of their granules into the peripheral circulation. APL is eminently.

Answer 38

is caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)

Answer 39

Features * Often none * Constitutional: anorexia, weight loss * Bleeding, infections * Lymphadenopathy more marked than CML

Answer 40

Complications * Hypogammaglobulinemia leading to recurrent infections → most common cause of death * Warm autoimmune hemolytic anemia in 10-15% of patients * Transformation to high-grade lymphoma (Richter's transformation)

Answer 41

* Progressive marrow failure: the development or worsening of anemia and/or thrombocytopenia * Massive (>10 cm) or progressive lymphadenopathy * Massive (>6 cm) or progressive splenomegaly * Progressive lymphocytosis: > 50% ↑ over 2 months or lymphocyte doubling time < 6 months * Systemic symptoms: weight loss > 10% in previous 6 months, fever >38oc for > 2 weeks, extreme fatigue, night sweats * Autoimmune cytopenias e.g. ITP

Answer 42

Immunophenotyping will demonstrate the cells to be B-cells (CD19 positive). CD5 and CD23 are also characteristically positive in CLL

Answer 43

None early on (when to start Rx is mentioned above) * Chlorambucil to ↓ lymphocyte count * Other options include fludarabine

Answer 44

♂Sex * Age > 70 years * Lymphocyte count > 50 * Prolymphocytes comprising > 10% of blood lymphocytes * Lymphocyte doubling time < 12 months * Raised LDH * CD38 expression positive

Answer 45

Hepatic veno-occlusive disease. It is a complication of high-dose chemotherapy given before a bone marrow transplant (BMT). The name sinusoidal obstruction syndrome is now preferred if VOD happens as a result of chemotherapy or bone marrow transplantation. Treatment is primarily supportive.

Answer 46

Features: * Fluid retention (weight gain, generalized edema, pleural effusion) * Hepatomegaly * ↑ Bilirubin (Jaundice) * Usually complicated by multi-organ failure

Answer 47

U/S abdomen helps in diagnosis * Liver biopsy shows centrolobar necrosis

Answer 48

rare malignant proliferation disorder of B cells lymphocytes. It is more common in ♂s (4:1) and is usually classified as a sub-type of chronic lymphoid leukemia. Hairy cells are abnormal WBCs with hair-like projections of cytoplasm.

Answer 49

Features * Pancytopenia (Monocytopenia is classical) * Splenomegaly * Skin vasculitis in 1/3 patients * 'Dry tap' despite bone marrow hypercellularity (also seen in myelofibrrosis) * Bone marrow biopsy migh show "fried egg appearance" * Tartrate resistant acid phosphotase (TRAP) stain positive

Answer 50

Management * Chemotherapy is first-line: cladribine, pentostatin * Immunotherapy is second-line: rituximab, interferon-α * Splenectomy sometimes required

Answer 51

causes damage and death by crowding out normal cells in the bone marrow, and by metastasizing. ALL is most common in childhood with a peak incidence at 2-5 years of age, and another peak in old age. The overall cure rate in children is ≈80%, and ≈45%-60% of adults have long-term disease-free survival. Acute → relatively short course of the disease (being fatal in as little as a few weeks if untreated)

Answer 52

Presentation: * Generalized weakness and fatigue * Anemia * Frequent or unexplained fever and infections * Weight loss and/or loss of appetite * Excessive and unexplained bruising * Bone pain, arthralgia. * Dyspnea due to lung infiltration. * Lymphandeopathy, hepatosplenomegaly. * Pitting edema in the lower limbs and/or abdomen * Petechiae due to thrombocytopenia

Answer 53

Diagnosis: * Leukocytosis. * Blast cells are seen on blood smear in 90% of cases * Bone marrow biopsy is conclusive proof of ALL * LP to detect CNS involvement. * CXR: to look for mediastinal mass (common in ALL). The Only MRCP Notes You’ll Ever Need 146 / 546 www.sudamedica.com * U&E to look for Tumor Lysis Syndrome. * Immunophenotyping, establish whether the "blast" cells origin is B or T lymphocytes * DNA testing; different mutations reflect prognosis.

Answer 54

Common ALL * Pre-B phenotype * Low initial WBC * FAB L1 type

Answer 55

* FAB L3 type * T or B cell surface markers * Philadelphia translocation, t(9;22) * Age < 2 years or > 10 years * ♂Sex. * CNS involvement * High initial WBC (e.g. > 100 * 109/l) * Non-Caucasian

Answer 56

left-shifted granulocytic series and nucleated red blood cells) with pancytopaenia. Also defined when there are immature cells (e.g myelocytes, and nucleated red blood cells) seen on the peripheral blood film.

Answer 57

↑ Bone marrow turnover e.g. in severe hemolytic anemia (in which case the reticulocyte count would be high). * Myelofibrosis and Chronic Myeloid Leukaemia (where there would be splenomegaly, and the white cell and platelet count would usually be raised). * Bone marrow invasion. Often in bone marrow invasion the invading malignancy will already have been diagnosed previously. * Myeloma * Polycythaemia Rubra Vera * Osteopetrosis * Tuberculous infiltration of the bone marrow * Sarcoidosis

Answer 58

is a malignant proliferation of lymphocytes characterized by the presence of the Reed-Sternberg cell. It has a bimodal age distributions being most common in the third and seventh decades. Hosgkin’s lymphoma is associated with EBV. 25% of patients have a constitutional upset, (night sweats, weight loss, fever, pruritus and lethargy)

Answer 59

Ann-Arbor staging of Hodgkin's lymphoma * I: single lymph node * II: 2 or more lymph nodes/regions on same side of diaphragm * III: nodes on both sides of diaphragm * IV: spread beyond lymph nodes

Answer 60

Age = 45 years * Stage IV disease * Hemoglobin < 10.5 g/dl * Lymphocyte count < 600/μl or < 8% *♂ * Albumin < 40 g/l * White blood count = 15,000/μ

Answer 61

MOST COMMON composed of large tumor nodules showing scattered lacunar classical RS cells background of - reactive lymphocytes - eosinophils and plasma cells with varying degress of collagen fibrosis/sclerosis.

Answer 62

common subtype is composed of - numerous classic RS cells - numerous inflammatory cells including lymphocytes, histiocytes, eosinophils, and plasma cells. Without sclerosis. This type is most often associated with EBV infection and may be confused with the early, so-called 'cellular' phase of nodular sclerosing CHL. Good

Answer 63

s a rare subtype, show many features which may cause diagnostic confusion with nodular lymphocyte predominant B-cell Non-Hodgkin's (B-NHL). Best prognosis

Answer 64

Rare + worse prognosis composed of large numbers of often pleomorphic RS cells with only few reactive lymphocytes which may easily be confused with diffuse large cell lymphoma. Many cases previously classified within this category would now be reclassified under anaplastic large cell lymphoma

Answer 65

Hodgkin results in patchy bone marrow infiltration, an isolated bone marrow biopsy may yield non-specific results. * Bone marrow biopsy is more useful for staging of advanced disease. * Lymph node biopsy would be more likely to be positive, Reed-Sternberg cell is evident on microscopy

Answer 66

The choice of treatment depends on the age, sex, bulk and the histological subtype of the disease. * Later disease (III, IVA, or IVB) are treated with combination chemotherapy alone. * Large mass in the chest (regardless of stage) are usually treated with combined chemotherapy and radiation therap. Chemo includes: Doxorubicin, Bleomycin, Vincristine, Cyclophosphamide and other cytotoxic drugs.

Answer 67

are a diverse group of lymphomas that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive. Low-grade lymphoma is predominantly a disease of older people. Most non-Hodgkin’s lymphomas are of B cell phenotype, though T cell tumours are increasingly being recognized.

Answer 68

* Most present with advanced disease, bone marrow infiltration being almost invariable. * Burkitt’s lymphoma is a high-grade lymphoma, which was first described in children in West Africa who presented with a jaw tumour, extra-nodal abdominal involvement and ovarian tumours. * Extra-nodal presentation is more common than Hodgkin's disease. * Renal impairment in non-Hodgkin’s lymphomas usually occurs as a consequence of ureteric obstruction secondary to intra-abdominal or pelvic lymph node enlargement. * Anaemia, an elevated white cell count and/or thrombocytopaenia are suggestive of bone marrow infiltration.

Answer 69

Management: * Lymph node biopsy is sufficient for a definitive diagnosis. * It is essential for modern classification to submit the lymphoid tissue for immuno-phenotyping and cytogenetic/molecular analysis. * High-grade lymphomas are responsive to chemotherapy and potentially curable, * Low-grade lymphomas are incurable with conventional therapy. * Chemotherapy is the mainstay of treatment in most cases.

Answer 70

high-grade B- cell neoplasm (NHL). There are two major forms: * Endemic (African) form: typically involves maxilla or mandible * Sporadic form: abdominal (ileo-caecal) tumors are the most common form. More common in patients with HIV

Answer 71

c-myc gene translocation, usually t(8:14). The Epstein- Barr virus (EBV) is strongly implicated in the development of the African form but the link to sporadic Burkitt's is less clear

Answer 72

This occurs after the initiation of a chemotherapeutic. TLS tends to occur in patients with bulky, rapidly proliferating, treatment-responsive tumors Association: * Acute leukemia * High-grade non-Hodgkin’ s lymphomas. * Pre-treatment ↑ LDH (levels of LDH correspond with tumor bulk)

Answer 73

Manifestation: rapid development (48-72 hours after initiation) of * ↑ kalemia (1st life-threatening abnormality) * ↑ uricemia * ↑ phosphatemia * ↓ calcemia * Acute renal failure.

Answer 74

Management: * Prevention is with good hydration before starting chemotherapy. * ↑ uricemia → urine alkalinisation and allopurinol * Osmotic diuretics are NOT first line therapy and may contribute to the precipitation of uric acid in the renal tubules. * Dietary modifications include restricting dietary potassium. *

Answer 75

Present in > 95% of patients with CML * This results in part of the Abelson (ABL) proto-oncogene being moved to the BCR gene on chromosome 22 * The resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal * Poor prognostic indicator in ALL and AML

Answer 76

* Seen in acute promyelocytic leukemia (M3) * Fusion of PML and RAR-α genes

Answer 77

* Seen in Burkitt's lymphoma * MYC oncogene is translocated to an immunoglobulin gene

Answer 78

Mantle cell lymphoma * Deregulation of the cyclin D1 (BCL-1) gene

Answer 79

Hodgkin's and Burkitt's lymphoma, nasopharyngeal carcinoma

Answer 80

Adult T-cell leukemia/lymphoma

Answer 81

gastric lymphoma (MALT)

Answer 82

Burkitt's lymphoma

Answer 83

required in patients receiving a bone marrow transplant, patients with previous purine analogue exposure and a diagnosis of Hodgkin’s disease.

Answer 84

should be used in patients who may need a bone marrow transplant in the future (since carriage of CMV increases transplant mortality).

Answer 85

Pulmonary causes * Asthma * Allergic bronchopulmonary aspergillosis * Churg-strauss syndrome * Loffler's syndrome * Tropical pulmonary eosinophilia * Eosinophilic pneumonia * Hypereosinophilic syndrome

Answer 86

Schistosomiasis * Nematodes: Toxocara, Ascaris, Strongyloides * Cestodes: Echinococcus

Answer 87

Drugs: sulfasalazine, nitrofurantoin * Psoriasis/eczema * Eosinophilic leukemia (very rare)

Answer 88

are unknown cause disease, occurring most commonly in ♂ in the 30-40-year-age group with persistent and markedly raised peripheral blood eosinophil count. Association: * Lung involvement may occur * Cardiovascular involvement with fibrosis and restrictive cardiomyopathy, which may lead to mural thrombus formation and considerable morbidity and mortality. * Angioedema or urticaria.

Answer 89

is with high dose corticosteroids (e.g. prednisolone 50mg which leads to a response in around 50% of cases). Steroid sparing agents such as cyclophosphamide or azathioprine may also be of some value.

Answer 90

very rare, is inherited in an autosomal recessive fashion, and tends to cause a mild/moderate bleeding disorder, although the phenotype does vary. Treatment is by factor replacement with plasma-derived products or using recombinant activated factor VII

Answer 91

Prothrombin time - prolonged Partial thromboplastin time - prolonged Bleeding time - unaffected

Answer 92

Prothrombin time - prolonged Partial thromboplastin time - prolonged Bleeding time - Prolonged

Answer 93

Prothrombin time - unaffected Partial thromboplastin time - prolonged Bleeding time - unaffected

Answer 94

Association: * Malignancy * Psoriasis * Pemphigus * Drugs: cephalosporins, penicillins

Answer 95

Diagnosis: * Bleeding tendencies * APTT: is prolonged (intrinsic pathway). * APTT doesn’t correct/will only correct slightly with the adding of normal plasma. * Bethesda titre can quantify the inhibitor. There is a 20% mortality rate from acquired factor VIII deficiency.

Answer 96

most common inherited thrombophilia It is due to a mutation in the Factor V Leiden gene. Heterozygotes have a 5-fold risk of venous thrombosis whilst homozygotes have a 50-fold ↑ risk. Any white pt aged <45 with thrombotic event should make you think of factor V Leiden mutation.

Answer 97

Von Willebrand's

Answer 98

X-linked genetic disorder involving a lack of functional clotting Factor VIII and represents 90% of Hemophilia cases

Answer 99

X-linked genetic disorder involving a lack of functional clotting Factor IX (Christmas disease) It is more severe but less common than Hemophilia A

Answer 100

Autosomal genetic (not X-linked) lack of functional clotting Factor XI. It is not completely recessive: heterozygous individuals also show ↑ bleeding

Answer 101

Association: * Autoimmune diseases: (Rheumatoid Arthritis or IBD) * Drugs such as phenytoin.

Answer 102

Management: * Where there are ↓ anti-factor VIII antibodies, factor VIII replacement may be all that is required. * Where bleeding is a serious problem then immunosupression with corticosteroids +/- steroid sparing agents such as cyclosporine may be required.

Answer 103

* Activated protein C resistance (factor V Leiden) * Antithrombin III deficiency * Protein C deficiency * Protein S deficiency

Answer 104

* Antiphospholipid syndrome * The Pill (COCP)

Answer 105

binding to antithrombin III, enhancing its anticoagulant effect by inhibiting the formation of thrombin and other clotting factors. Patients with antithrombin III deficiency may therefore by resistant to heparin treatment

Answer 106

an inherited cause of thrombophilia occurring in approximately 1:2,000 of the population. Inheritance is autosomal dominant Antithrombin III inhibits several clotting factors, primarily thrombin, factor X and factor IX. It mediates the effects of heparin Antithrombin III deficiency comprises a heterogeneous group of disorders, with some patients having a deficiency of normal antithrombin III whilst others produce abnormal antithrombin III

Answer 107

Features * Recurrent venous thromboses * Arterial thromboses do occur but is uncommon Management * Thromboembolic events are treated with lifelong warfarinisation * Heparinisation during pregnancy* * Antithrombin III concentrates (often using during surgery or childbirth) *as patients with antithrombin III deficiency have a degree of resistance to heparin anti-Xa levels should be monitored carefully to ensure adequate anticoagulation

Answer 108

Management * Thromboembolic events are treated with lifelong warfarinisation * Heparinisation during pregnancy* * Antithrombin III concentrates (often using during surgery or childbirth) *as patients with antithrombin III deficiency have a degree of resistance to heparin anti-Xa levels should be monitored carefully to ensure adequate anticoagulation

Answer 109

most common inherited bleeding disorder. The majority of cases are inherited in an autosomal dominant fashion* and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst hemoarthroses and muscle hematomas are rare. Role of von Willebrand factor * Large glycoprotein which forms massive multimers up to 1,000,000 Da in size * Promotes platelet adhesion to damaged endothelium * Carrier molecule for factor VIII

Answer 110

:Type1 partial reduction in vWF (80% of patients) * type 2: abnormal form of vWF * type 3: total lack of vWF (autosomal recessive) most sev

Answer 111

Presentation: * Petechial skin * Slightly elevated APTT * ↓ factor VIII activity

Answer 112

Investigation * Prolonged bleeding time * APTT may be prolonged * Factor VIII levels may be moderately ↓ * Defective platelet aggregation with ristocetin

Answer 113

Management * Tranexamic acid for mild bleeding * Desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells. Used as prohyplaxis prior to procedures. * Factor VIII concentrate

Answer 114

Causes of severe thrombocytopenia * ITP * TTP * DIC * Hematological malignancy

Answer 115

Causes of moderate thrombocytopenia * Heparin induced thrombocytopenia (HIT) * Drug-induced (e.g. quinine, diuretics, sulphonamides, aspirin, thiazides) * Alcohol and Vitamin B12 deficiency * Liver disease * Hypersplenism * Viral infection (EBV, HIV, hepatitis) * Pregnancy * SLE/antiphospholipid syndrome

Answer 116

immune mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb-IIIa or Ib complex. ♀:♂=2.6:1. Common cause of death is bleeding (mainly intracranial).

Answer 117

Investigations * Antiplatelet autoantibodies (usually IgG) * Bone marrow aspiration shows megakaryocytes in the marrow. This should be carried out prior to the commencement of steroids in order to rule out leukemia

Answer 118

Management * Oral prednisolone (80% of patients respond) * Splenectomy if platelets < 30 after 3 months of steroid therapy * IV immunoglobulins * Immunosuppressive drugs e.g. Cyclophosphamide

Answer 119

More commonly seen in children o Equal sex incidence o May follow an infection or vaccination o Usually runs a self-limiting course over 1-2 weeks

Answer 120

More common in young/middle-aged women o Tends to run a relapsing-remitting course

Answer 121

ITP in association with autoimmune hemolytic anemia (AIHA)

Answer 122

not commonly seen in TTP. It occurs more commonly in conditions such as antiphospholipid syndrome and cholesterol embolism

Answer 123

Neuro signs and purpura point towards TTP

Answer 124

Pathogenesis of thrombotic thrombocytopenic purpura (TTP) * Abnormally large and sticky multimers of vWF cause platelets to clump within vessels * In TTP there is a deficiency of caspase which breakdowns large multimers of vWF. * Overlaps with hemolytic uraemic syndrome (HUS)

Answer 125

Features * Rare, typically adult ♀ * Fever * Fluctuating neuro signs (microemboli) * Microangiopathic hemolytic anemia * Thrombocytopenia * Renal failure

Answer 126

Causes * Post-infection e.g. Urinary, gastrointestinal * Pregnancy * Drugs: cyclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir * Tumors * SLE * HIV

Answer 127

anagement * No antibiotics - may worsen outcome * Plasma exchange is the treatment of choice * Steroids, immunosuppressants * Vincristine

Answer 128

Cytotoxics * Antibiotics: trimethoprim, chloramphenicol * Anti-rheumatoid: gold, penicillamine * Carbimazole* * Anti-epileptics: carbamazepine * Sulphonylureas: tolbutamide

Answer 129

severe immune-mediated drug reaction that can occur in patients receiving unfractionated heparin (at full therapeutic doses and low prophylactic doses, including the minute amounts in heparin flushes and on heparin-coated catheters) and those receiving low-molecular weight heparin (LMWH). Antibodies usually develop after a patient has been on heparin for five or more days, but may develop sooner if there has been previous heparin exposure.

Answer 130

HIT is strongly associated with thrombosis. Thromboembolic complications can be venous, arterial, or both, and include: * DVT * Pulmonary embolism * Myocardial infarction * Thrombotic stroke * Occlusion of limb arteries.

Answer 131

* Type I: usually occurs 48 to 72 hours post commensing heparing and PLT rarely < 100. PLT returns to normal over 4 days and there is no ↑ risk of thromboembolism * Type II: much rarer and usually occurs 5 to 10 days after starting heparin, PLT usually <100, patients are at ↑ risk of thromboembolic events. Heparin products should be stopped and the patient commenced on alternative medication

Answer 132

Stop all forms of Heparin * Start alternative anticoagulant which do not cross-react with HIT antibodies, such as: o Danaparoid o Lepirudin o Argatroban. * Oral anticoagulation with warfarin should NOT be initiated for longer-term protection from further events until substantial platelet count recovery has occurred. HIT patients who are switched to warfarin alone after the discontinuation of heparin may paradoxically have worsening thrombosis and develop venous limb gangrene and skin necrosis.

Answer 133

Target cells * Howell-Jolly bodies * Cabot's rings * Siderotic granules * Acanthocytes * Schizocytes

Answer 134

* Target cells * 'Pencil' poikilocytes * If combined with B12/folate deficiency a 'dimorphic' film occurs with mixed microcytic and macrocytic cells

Answer 135

Heinz bodies

Answer 136

* 'Tear-drop' poikilocytes

Answer 137

* Schistocytes

Answer 138

* Hypersegmented neutrophils

Answer 139

Splenic lymphoma with villous lymphocytes

Answer 140

Follicular lymphoma

Answer 141

Always +ve in hairy cell leukaemia

Answer 142

acute myeloblastic leukaemia

Answer 143

acute lymphoblastic leukaemia

Answer 144

↑ in polycythemia RV and myelofibrosis ↓ in chronic myeloid leukaemia

Answer 145

Also known as Osler-Weber-Rendu syndrome, hereditary hemorrhagic telangiectasia is an autosomal dominant condition characterized by (as the name suggests) multiple telangiectasia over the skin and mucous membranes. 20 % of cases occur spontaneously without prior family history.

Answer 146

Epistaxis * Telangiectasia develop ob skin, mucous membranes and internal organs * Associated with pulmonary and other AV malformations in 10% * May present as iron-deficiency anemia secondary to bleeding in the GI tract or nasal mucosa

Answer 147

Features: * Monoclonal IgM paraproteinemia * Systemic upset: weight loss, lethargy * Hyperviscosity syndrome e.g. Visual disturbance * Hepatosplenomegaly * Lymphadenopathy * Cryoglobulinemia e.g. Raynaud's * ↑ESR

Answer 148

anagement: * Alkylating agents * Young patient may benefit from doxorubicin. * Treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or Vincristine or with thalidomide. * Corticosteroids, such as Prednisone, may also be used in combination. * Plasmapheresis can be used to treat the hyperviscosity (it does not address the underlying disease)

Answer 149

One of the key differentiating features between (MGUS) and myeloma is the absence ofcomplications such as immune paresis, hypercalcemia and bone pain Differentiating features from myeloma * Normal immune function * Normal β-2 microglobulin levels * Lower level of paraproteinemia than myeloma (e.g. < 30g/l IgG, or < 20g/l IgA) * Stable level of paraproteinemia * No clinical features of myeloma (e.g. Lytic lesions on x-rays or renal disease)

Answer 150

Serum paraprotein <30 g/L AND * Clonal plasma cells <10% on bone marrow biopsy AND * NO myeloma-related organ or tissue impairment

Answer 151

Methemoglobinemia = oxidation of Fe2+ in hemoglobin to Fe3+ Hemoglobin which has been oxidised from Fe++ (Ferrous) to +++ Fe . This is normally regulated by NADH methemoglobin reductase, which transfers electrons from NADH to methemoglobin resulting in the reduction of methemoglobin to hemoglobin. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxidation dissociation curve is moved to the left

Answer 152

Congenital causes * Hemoglobin chain variants: HbM, HbH * NADH methemoglobin reductase deficiency cquired causes * Drugs: sulphonamides, nitrates, dapsone, sodium nitroprusside, primaquine * Chemicals: aniline dyes

Answer 153

Features * 'Chocolate' cyanosis * Dyspnea, anxiety, headache * Severe: acidosis, arrhythmias, seizures, coma * Normal PO2 but ↓ oxygen saturation

Answer 154

Management * NADH - methemoglobinemia reductase deficiency: ascorbic acid * IV methylene blue if acquired

Answer 155

Autosomal recessive * Aplastic anemia * ↑ risk of AML * Neurological manifestation * Skeletal abnormalities * Skin pigmentation (café-au-lait spots)

Answer 156

General population: transferrin saturation > ferritin * Family members: HFE genetic testi

Answer 157

is an autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation. It is caused by inheritance of mutations in the HFE gene on both copies of chromosome 6*. The British Committee for Standards in Hematology (BCSH) published guidelines for the investigation and management of hemochromatosis in 2000

Answer 158

Molecular genetic testing for the C282Y and H63D mutations * Liver biopsy: Perl's stain

Answer 159

Early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands) * 'Bronze' skin pigmentation * Diabetes Mellitus * Liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition. * Cardiac failure (2nd to dilated cardiomyopathy) * Hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism) * Arthritis (especially of the hands)

Answer 160

Reversible complications Cardiomyopathy * Skin pigmentation

Answer 161

* Liver cirrhosis** * Diabetes mellitus * Hypogonadotrophic hypogonadism * Arthropathy

Answer 162

Vaccination * If elective, should be done 2 weeks prior to operation * Pneumococcal, HIB, meningitis A & C and annual influenza vaccination Antibiotic prophylaxis * Penicillin V: unfortunately clear guidelines do not exist of how long antibiotic prophylaxis should be continued. It is generally accepted though that penicillin should be continued for at least 2 years and at least until the patient is 16 years of age, although the majority of patients are usually put on antibiotic prophylaxis for life

Answer 163

Causes * Splenectomy * Sickle-cell * Coeliac disease, dermatitis herpetiformis (HLA DR3) * Graves' disease * SLE * Amyloid

Answer 164

Supportive * Blood products * Prevention and treatment of infection Anti-thymocyte globulin (ATG) and anti-lymphocyte globulin (ALG) * Prepared in animals (e.g. Rabbits or horses) by injecting human lymphocytes * Is highly allergenic and may cause serum sickness (fever, rash, arthralgia), therefore steroid cover usually given * Immunosuppression using agents such as Cyclosporin may also be given Stem cell transplantation * Allogeneic transplants have a success rate of up to 80%

Answer 165

Megaloblastic causes: * Vitamin B12 deficiency * Folate deficiency * Cytotoxics e.g. Hydroxyurea

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Normoblastic causes: * Alcohol * Liver disease * Hypothyroidism * Pregnancy * Reticulocytosis e.g. Hemolysis * Aplastic anemia * Myelodysplasia * Drugs: cytotoxics

Answer 167

hemoglobinopathy resulting from defective synthesis of globin chains required for hemoglobin synthesis. Each copy of chromosome 16 has two genes for the alpha globin subunit (four in total), and each copy of chromosome 11 has one gene for the beta subunit (two in total). Adult hemoglobin HbA(α2β2), second adult hemoglobin HbA2(α2δ2), fetal hemoglobin HbF(α2γ2).

Answer 168

due to a deficiency of α chain in hemoglobin * 2 separate α-globulin genes are located on each chromosome 16 * Clinical severity depends on the number of α chains present * If 1 or 2 α chains are absent then the blood picture would be hypochromic and microcytic, but the Hb level would be typically normal * Loss of 3 α chains results in a hypochromic microcytic anemia with splenomegaly. This is known as HbH disease * If all 4 α chains absent (i.e. homozygote) then death in utero (hydrops fetalis, Bart's hydrops) o 1 gene deletion: silent carrier o 2 gene deletion: α-thalassaemia trait (microcytosis, +/- anemia, decreased HbA2) o 3 gene deletion: hemoglobin H disease (β4)-moderate anemia, splenomegaly o 4 gene deletion: Bart’s hemoglobin(γ4) - hydrops fetalis

Answer 169

HbB gene on chromosome 11, autosomal-recessive fashion. 1 gene deletion: β-thalassaemia minor (mild anaemia, microcytosis, elevated HbA2) o 2 gene deletion: β -thalassaemia major (anaemia when HbF tries to convert to HbA during first year of life, extramedullary hemopoiesis with hepatosplenomegaly and bone marrow expansion, ‘hair on end’ appearance of bone).

Answer 170

As well as alpha and beta chains being present in hemoglobin about 3% of adult hemoglobin is made of alpha and delta chains. Just as with beta thalassemia, mutations can occur which affect the ability of this gene to produce delta chains.

Answer 171

Hemoglobin E/thalassemia: common in Cambodia, Thailand, and parts of India; clinically similar to β thalassemia major or thalassemia intermedia. * Hemoglobin S/thalassemia, common in African and Mediterranean populations; clinically similar to sickle cell anemia, with the additional feature of splenomegaly * Hemoglobin C/thalassemia: common in Mediterranean and African populations, hemoglobin C/βo thalassemia causes a moderately severe hemolytic anemia with splenomegaly; hemoglobin C/β+ thalassemia produce a milder disease.

Haemotolgy Flashcards

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