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Medicine - Year 2 > The haematological system and skin - Coagulation and the bone marrow in health and disease > Flashcards

The haematological system and skin - Coagulation and the bone marrow in health and disease Flashcards

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1
Q

Thrombophilias - who should be screened

A

Patients with thrombosis who are young

Positive family history

Thrombosis in an unusual site

Recurrence

Females with recurrent foetal loss

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2
Q

Inherited thrombophilias

A

Factor V Leiden

Protein C deficiency

Protein S deficiency

Antithrombin III deficiency

Prothrombin mutation

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3
Q

Acquired thrombophilia

A

Oestrogen therapy, contraceptive pill

Malignancy

Pregnancy and puerperium

Lupus anticoagulant (antiphospholipid) syndrome

Raised plasma homocysteine (may also be inherited)

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4
Q

Lupus anticoagulant (antiphospholipid) syndrome - clinical features

A

CLOT

Clots: arterial/venous thrombosis

Lived reticularis

Obstretic loss: recurrent miscarriages

Thrombocytopenia

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5
Q

Lupus anticoagulant (antiphospholipid) syndrome - laboratory features

A

Prolonged APTT

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6
Q

Lupus anticoagulant (antiphospholipid) syndrome - Management

A

Lifelong anticoagulation

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7
Q

Management of warfarin - major bleeding

A

Stop warfarin

Administer IV vitamin K

Administer prothrombin complex ( or fresh frozen plasma if prothrombin complex unavailable)

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8
Q

Management of warfarin - minor bleeding

A

Stop anticoagulants

Administer IV vitamin K

Repeat INR after 24 hours, may need further vitamin K

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9
Q

Management of warfarin - no bleeding with INR > 8

A

Stop anticoagulants

Administer IV or oral vitamin K

Repeat INR after 24 hours

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10
Q

Management of warfarin - no bleeding with INR between 5-8

A

Withhold 1-2 doses of warfarin and restart at reduced dose

Review maintenance dose of warfarin

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11
Q

Heparin - management of over anticoagulation/bleeding

A

Stop heparin – short half-life, may be sufficient

Local measures e.g., apply pressure

Consider tranexamic acid

If bleeding, consider protamine sulphate

Look for cause e.g., incorrect dose, new renal failure

Before restarting check risk: benefit ratio

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12
Q

DOAC - management of anticoagulation/bleeding

A
  • Stop DOAC
  • Local measures e.g., apply pressure
  • Consider tranexamic acid

Idracruzimab reveral agent for dabigatran

  • Antidote to Xa inhibitors not yet available. In the meantime, in life threatening bleeding consider prothrombin complex concentrate
  • Look for cause
  • Before restarting check risk:benefit ration
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13
Q

Warfarin: risk factors for bleeding

A
  • Elderly
  • Renal failure
  • Liver failure
  • Recurrent falls
  • Platelet of NSAIDs use
  • Alcoholism
  • Cancer
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14
Q

Leucocytosis - causes

A

Primary
- Leukaemia/ lymphoma/ myeloproliferative disorders

Secondary
- infection
- Inflammation
- Infarction
- Tumour

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15
Q

Thrombocytosis - causes

A

Primary - essential thrombocythemia

Secondary
- Infection
- Inflammation
- Infarction
- Tumour

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16
Q

Essential thrombocythemia - aetiology and pathophysiology

A

JAK2 mutation in 50% cases

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17
Q

Essential thrombocythemia - clinical features

A

Asymptomatic - at least 30%

Thrombosis (arterial/venous)

Headaches, visual disturbances

Excessive haemorrhage may occur spontaneously or after trauma or surgery

Pruritis and sweating are uncommon

Gout (raises uric acid)

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18
Q

Essential thrombocythemia - laboratory features

A

Raised platelet count

Raised red cell and/or white cell in 30%

Blood film - platelet anisocytosis with circulating megakarocyte fragments. Auto infraction of the spleen may case target cells, Howell-Jolly bodies

JAK2 mutation

Raised serum uric acid

Serum LDH normal

Bone marrow - hyper cellular + increased megakarocytes

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19
Q

Essential thrombocythemia - management

A

Aspirin only in younger patients < 40 years

Chemotherapy with hydroxycarbamide + aspirin in > 40 years

Alpha interferon (may be used in younger patients but needs injections and has side- effects - flu like symptoms)

Allopurinol for gout

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20
Q

True erythrocytosis “polycythaemia” - definition and causes

A

Definition
- Increased number of red cells

Causes
- Primary: Polycythaemia rubra vera
- Secondary: low oxygen e.g., cold, tumours, doping, high affinity haemoglobin

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21
Q

Apparent erythrocytosis - defenition and causes

A

Definition
- Reduced plasma volume

Causes
- Smoking
- Overweight
- Alcohol excess
- Medications e.g., diuretics

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22
Q

Polycythaemia rubra vera - aetiology and pathophysiology

A

Mutations of JAK2 in > 995% cases

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23
Q

Polycythaemia rubra vera - clinical features

A
  • Aquagenic pruritus (itchiness after hot bath especially)
  • ‘Ruddy complexion’/plethora/redness
  • Teaches and visual disturbances
  • Thrombosis (arterial/venous)
  • Haemorrhage especially GI
  • Splenomegaly
  • Hyperviscosity symptoms: chest pain, myalgia, weakness, headache, blurred vision, loss of concentration
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24
Q

Polycythaemia rubra vera - Laboratory features

A
  • Raised hb, haemoatocrit and red cell count
  • Raised white cells and/or platelets (in 75% people)
  • JAK2 mutation
  • Raised serum uric acid
  • Serum LDH normal or slightly raised
  • Low serum EPO (to prevent further erythrocytosis)
  • Hypercellular bone marrow with deplete iron stores
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25
Polycythaemia rubra vera - management
Venesection +/- chemotherapy with oral hydroxycarbamide + aspirin Plasmapheresis for hyperviscosity syndrome PPI for patients with indigestion or history of GI bleeding Allopurinol to prevent hyperuricemia
26
Polycythaemia rubra vera - prognosis
Development of myelofibrosis (in up to 30% AML (in ups o 5%, not increased by hyrdoxycarbamide)
27
Thrombocytopenia - causes
Underproduction - Drugs affect stem cell - Liver failure - Part of pancytopenia due to marrow failure Peripheral destruction - Autoimmune (ITP) - Hypersplenism - Drugs - Infection/inflammation/ sepsis
28
Low blood counts caused by reduced production - causes
Myeloma Myelodysplasia Metastatic malignancy Myelofibrosis Leukaemia Lymphoma Aplastic anaemia Haematinic deficiency
29
Immune thrombocytopenia purpura (ITP) - definition
Autoimmune disease of Unkown cause where the number of platelets is reduced
30
Immune thrombocytopenia purpura (ITP) - clinical features
Isolated thrombocytopenia: - On incidental finding or - Features of purpura or - Other minor bleeding
31
Immune thrombocytopenia purpura (ITP) - management
Oral prednisolone - patients with a platelet of <30 × 10^9/L or a platelet count >30 × 10^9/L and features of minor bleeding/high risk Splenectomy - refractory cases Avoid platelet transfusions in the absence of life-threatening bleeding
32
Myelodysplasia (myelodysplastic syndrome) - definition
Haematopoietic stem cell malignancy where there is abnormal maturation as well as proliferation of cells in bone marrow. It is characterised by peripheral blood cytopenia
33
Myelodysplasia (myelodysplastic syndrome) - Aetiology and pathogenesis
May be primary or secondary, as. consequence of a previous chemotherapy/radiotherapy
34
Myelodysplasia (myelodysplastic syndrome) - laboratory findings
Macrocytic anaemia Pancytopenia Blood film - Active, cellular marrow
35
Myelodysplasia (myelodysplastic syndrome) - differential diagnosis
Other causes of anaemia must be excluded Myelofibrosis Aplastic anaemia
36
Myelodysplasia (myelodysplastic syndrome) - management
Supportive care with red cell or platelet transfusion and antimicrobials may be required Erythropoietin Iron chelation theory to prevent iron overload Chemotherapy Allogenic stem cell transplant (may cure younger patients)
37
Aplastic anaemia - definition
Chronic pancytopenia associated with hypoplastic bone marrow
38
Aplastic anaemia - aetiology and pathogenesis
May be acquired or congenital (e.g., Fanconi's anaemia), dyskeratosis congenital
39
Aplastic anaemia - epidemiology
May occur at any age, in either sex
40
Aplastic anaemia - Clinical features
Onset rapid (over few days) or slow (over weeks or months Liver, spleen and lymph nodes not enlarged
41
Fanconi's anaemia - genetic inheritance
Autosomal recessive
42
Fanconi's anaemia - clinical features
- Presents in childhood - Pigmentation abnormalities - Hearing defects - Renal abnormalities - Genital abnormalities - Solid tumours - Short stature
43
Aplastic anaemia - laboratory findings
Normocytic anaemia or mild microcytic with a low reticulocyte Pancytopenia Blood film- hypo plastic with > 75% fat spaces ("empty" bone marrow)
44
Aplastic anaemia - management
Immunosuppression Androgens Stem cell transplantation is a cure in severe cases Haemopoietic growth factors, granulocyte colony-stimulating factor may raise neutrophil count temproily Blood product support
45
Myelofibrosis - aetiology and pathophysiology
Malignant proliferation of reticulin fibres in bone marrow causing anemia,
46
Myelofibrosis - epidemiology
Sexes affected equally > 50 years
47
Myelofibrosis - clinical features
Frequent - fever, weight loss, pruritus, hepatomegaly and night sweats Less common - gout, bone and joint pain Late stages - abdominal swelling, ascites and bleeding from oesophageal varicose occur
48
Myelofibrosis - laboratory features
Normochromic normocytic anaemia Leucocytosis and thrombocytosis occur early, and later leucopenia and thrombocytopenia Blood film: red cell poikilocytes with teardrop forms JAK2 mutation in 50% cases LDH raise (unliked in PRV and ET) LFTs are often abnormal because of extramedullary haemopoiesis "Dry tap" on attempt of bone marrow aspiration
49
Myelofibrosis - management
- Chemotherapy with hydroxycarbamide - JAK2 inhibitors - Thalidomide - improves marrow function and reduces spleen size - Supportive therapy with red cell transfusions, folic acid and occasionally platelett transfuion - Iron chelation to prevent iron overload - Splenectomy or splenic irradiation - Allogenic stem cell transplantation: a cure for younger patients
50
Myelofibrosis - prognosis
Can transform into acute lymphoblastic leukaemia
51
Hyposplenism - causes
Splenectomy Auto-infarction e.g., sickle cell disease infiltration - metastatic malignancy Under-function - coeliac disease
52
Neutrophilia - causes
Primary - Myeloproliferative disorder e.g., chronic myeloid leukaemia Secondary - Bacterial infection - Inflammatory conditions - Burns - Cigarette smoking - Steroids - G-CSF - Solid tumour
53
Lymphocytosis - causes
Viral infection e.g., EBV Hyposplenism TB Brucellosis Chronic lymphocytic leukaemia (CLL) Lymphoma with 'spill over'
54
Eosinophilia - causes
Allergic reactions Vasculitis Drus Worm infestations Cancer (especially solid tumours and lymphoma)
55
High grade lymphomas - characteristics
- Short history - Grows quickly - Patiently usually symptomatic - Treatment always required immediately - Potentially curable - Treatment intensive chemotherapy - Once chance to cure (or maybe two)
56
Low grade lymphomas - characteristics
- Often longer or 'no' history - Grows slowly - Patients often asymptomatic - Treatment often not required (watch and wait) - A lifelong illness - Treatment generally less intensive chemotherapy - Can usually treat again and again...
57
Lymphomas - clinical features
58
Hodgkin lymphoma - epidemiology
Males > females Most common in young adults and over 60s
59
Hodgkin lymphoma - histological classification
Characterised by the presence of reed-sterner cells
60
Hodgkin lymphoma - types
1. Classical - Nodular sclerosis - Mixed cellularity - Lymphocytic-rich - Lymphocytic-deplete 2. Nodular lymphocyte-predominant
61
Hodgkin lymphoma - clinical features
Lymphadenopathy - painless, alcohol may precipitate pain 'B' symptoms - fever, night sweats and weight loss (unexplained, > 10% in 6 months) Mediastinal mass Pruritus Splenomegaly/hepatosplenomegaly Malaise Fatigue Extra nodal disease - lung, CNS, skin and bone involvement
62
Hodgkin lymphoma - investigations
Bloods - FBC - U&eS, Bone profile, LDH, Uric acid, ESR Imaging - CXR - PET CT: used in staging of disease - CT neck, chest, abdomen and pelvis - MRI Additional - Lumbar puncture and CSF analysis: in those with suspected CNS disease - Echocardiogram - Pulmonary function tests - Bone marrow biopsy
63
Hodgkin lymphoma - laboratory features
- Anaemia (normochromic, normocytic; AIHA can occur) - Leucocytosis - Raised ESR - Raised LDL - Abnormal LFTs
64
Hodgkin lymphoma - staging used
Ann Arbour staging
65
Describe Ann Arbor staging
Stage I - single lymph node region Stage 2 - two or more lymph node regions on the same side of the diaphragm Stage 3 - two or more lymph node region above and below the diaphragm Stage 4 - widespread disease; multiple organs with out with lymph node involvement A: absence of B symptoms B: fever, nights sweats and weight loss
66
Hodgkin lymphoma - management
Chemotherapy
67
Non-hodgekin lymphoma - histological classification
Characterised by no reed-sternberg cells
68
Non-hodgkin lymphoma - presentation
Lymphadenopathy 'B' symptoms - fever, night sweats and weight loss (unexplained, > 10% in 6 months) Pruritus Splenomegaly Hepatomegaly
69
Non-hodgkin lymphoma - investigations
Bloods – FBC, U&Es, LFTs, Bone profile, LDH, Uric acid, ESR, Imaging - CXR - PET CT: Used in the staging of disease - CT neck, chest abdomen and pelvis - MRI brain - Bone scan Additional - Lumbar puncture and CSF analysis: in those with suspected CNS disease - Bone marrow aspirate and biopsy
70
Non-hodgkin lymphoma - investigations - laboratory features
Anaemia or pancytopenia Peripheral blood lymphocytosis Paraprotein (especially in lymphoplasmacytic lymphoma) or hypogammaglobinaemia Serum LDH raised in more aggressive forms Raised serum B2-microglobulin
71
Non-hodgkin lymphoma - staging used
Ann arbour staging
72
Non-hodgekin lymphoma - high-grade lymphomas examples
Diffuse large b-cell lymphoma Burkitt lymphoma
73
Burkitt's Lymphoma - appearance on biopsy
'Starry' appearance
74
What type of non-hodgekin lymphoma is associated with Helicobacte Pylorir?
Gastric MALT (mucosa-associated lymphoma tissue
75
What types of non-hodgekin lymphoma is associated with EBVr?
Burkitt's lymphoma (AIDS-related CNS lymphoma)
76
What types of Non-hodgekin lymphoma is associated with hepatitis C
Large B-cell lymphoma (Splenic marginal zone lymphoma)
77
Non-hodgekin lymphoma - management
Chemotherapy

Medicine - Year 2 (27 decks)

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