Haematology Flashcards

1
Q

When should you suspect neutropenic sepsis?

  • neutrophils < x?
  • or new onset: ?
A
  • in a neutropenic pt (<1x10^9) who is pyrexial

- or has new-onset confusion, tachycardia, HT, dyspnoea, or hypothermia

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2
Q

what sites should you examine when assessing a pt with suspected neutropenic sepsis:

A

-mucous membranes
-oropharynx (?thrush, erythema)
-surgical sites
-IV lines and other lines
NB: should swab and send for microscopy from all suspicious areas

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3
Q

Acute neutropenic sepsis management is start empirical IV abx e.g. _____ and aminoglycoside to cover gram __ and _______.

  • if clinical deterioration/fever persists/suspected MRSA what abx should you add?
  • when to swap to oral and continue for how long?
A
  • empirical IV abx e.g. piperacillin
  • cover gram negative and pseudomonas
  • add Vancomycin
  • swap to oral when apyrexial for 48hrs and continue for 10-14days
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4
Q

Suggest 5 causes of a neutropenia?

A
  • african race
  • viral infection
  • severe bacterial infection
  • megaloblastic anaemia
  • pancytopenia
  • drugs causing marrow aplasia or immune destruction
  • inherited abnormalities
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5
Q

What happens in DIC?

A
  • widespread fibrin generation in blood vessels caused by initiation of the coagulation pathway
  • platelets and coagulation factors are consumed and fibrinolysis is activated secondarily
  • leads to FDPs production that contribute to bleeding by inhibiting fibrin polymerisation
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6
Q

Suggest 2 triggers for DIC?

A
  • release or expression of tissue factor
  • extensive damage to vascular endothelium exposing TF or enhanced expression of TF by monocytes in response to cytokines
  • sepsis
  • major trauma
  • tissue destruction (surgery, severe burns)
  • advanced cancer
  • obstetric complications (amniotic fluid embolism, abruptio placentae)
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7
Q

Why does DIC occur often in acute promyelocytic leukaemia?

A

-due to generation of procoagulant substances in the blood

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8
Q

Presentation of DIC is variable on a spectrum, suggest how it may present?

A
  • no bleeding —> complete haemostatic failure (bleeding from venepuncture sites, nose, mouth….)
  • thrombotic events occur due to vessel occlusion by platelets and fibrin
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9
Q

What investigations would you arrange in DIC and suggest their findings?

A
  • prolonged PT, APPT and TT
  • decreased fibrinogen
  • elevated fibrin degradation products (FDPs)
  • blood film: fragmented red cells
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10
Q

In chronic/mild cases of DIC, blood results (PT, APPT, TT) can be largely unremarkable or only show an in increase in the ___ reflecting accelerated ____

A
  • FDPs (like D Dimers)

- accelerated fibrinolysis

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11
Q

DIC can be caused by: -vascular endothelium damage, exposed/increased TF by monocytes, sepsis, trauma, cancer, obstetric complications.. how is it treated?-

A

treat underlying condition, then for pts that are bleeding give:

  • platelet concentrates to maintain count (>50x10^9)
  • FFP
  • cryoprecipitate
  • red cell concentrated
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12
Q

Neutrophil leukocytosis (>10x10^9) suggest 4 causes:

A
  • bacterial infection
  • tissue necrosis
  • inflammation
  • corticosteroid therapy
  • myeloproliferative disease
  • acute haemorrhage, haemolysis
  • leukemoid reaction (characterised by immature white cells in peripheral blood)
  • leucoerythroblastic anaemia
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13
Q

Multiple myeloma is a malignant disease of which cells?

-clonal proliferation of these cells results in what in the blood/urine?

A
  • The plasma cells of bone marrow
  • Clonal proliferation of bone marrow plasma cells usually capable of producing monoclonal immunoglobulins (paraproteins) mostly IgG or IgA.
  • Result is paraproteinaemia may be associated with excretion of light chains in urine
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14
Q

Multiple myeloma presents at average age of 60yrs

  • the clinical features arise from it’s result on bone, kidneys and blood
  • explain the issues with the bones:
A
More osteoclast activity -> 
-bone pain esp. back pain, 
-osteolytic lesions, 
-pathological fractures, 
-spinal cord compression 
-hypercalcaemia
BM infiltration with plasma cells --> anaemia, infections, bleeding
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15
Q

Multiple myeloma presents at average age of 60yrs

  • the clinical features arise from it’s result on bone, kidneys and blood
  • explain the issues it causes with the kidney:
A

AKI due to:

  • deposition of light chains in tubules
  • hypercalcemia
  • hyperuricemia
  • amyloid deposition
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16
Q

Multiple myeloma presents at average age of 60yrs

  • the clinical features arise from it’s result on bone, kidneys and blood
  • explain the issues it can cause with the blood? leading to what sorts of symptoms?
A
  • paraproteins can form aggregates in the blood which greatly increase the viscosity leading to: blurred vision, gangrene and bleeding
  • infections occur due to a reduction of normal polyclonal immunoglobulin levels (immune paresis)
17
Q

Investigating multiple myeloma

-requires 2 out of 3 diagnostic features to be present, what are these?

A
  • paraproteinaemia on serum protein immunofixation / Bence Jones protein in urine
  • CT/MRI evidence of lytic bone lesions
  • increase in BM plasma cells on BM aspirate or trephine biopsy
18
Q

Diagnosis of multiple myeloma:

-requires 2 out of 3 diagnostic features to be present, what are these?

A
  • paraproteinaemia on serum protein immunofixation / Bence Jones protein in urine
  • CT/MRI evidence of lytic bone lesions
  • increase in BM plasma cells on BM aspirate or trephine biopsy
19
Q

Diagnosing MM requires 2+/3 of the following:
-monoclonal protein band in serum/urine electrophoresis
-CT/MRI evidence of lytic bone lesions
-increase in BM plasma cells on BM aspirate or trephine biopsy
-end organ damage evidence e.g. renal insufficiency, highCa2+, anaemia
What other investigations should be sent for multiple myeloma

A
  • blood count (may show anaemia, thrombocytopenia and leukopenia)
  • ESR is often high, blood film shows rouleux
  • serum biochem may show renal failure and hypercalcaemia

(NB: serum beta2-microglobulin and albumin are used in prognosis)

20
Q

How is multiple myeloma managed? What does supportive treatment entail? Prognosis

A
  • supportive care (correct anaemia w transfusion/erythropoietin, treat infections promptly, treat bone pain with radiotherapy or high dose dexamethasone)
  • treat AKI/hypercalcaemia with adequate hydration
  • bisphosphonates to reduce progression of bone disease
  • treat hyperviscosity by plasmapheresis + systemic therapy
  • chemotherapy, autologous stem cell transplant. An alkylator e.g. cyclophosphamide, melphalan steroid and novel agent e.g. bortezomib/lenalidomide.
  • survival 5-10yrs (incurable currently)
21
Q

Name 2 complications post splenectomy:

In conjunction with this name 2 preventative measures that are given:

A
  • thrombophilia in the short term (mobilise early post-op)
  • acute gastric dilatation
  • sepsis/infection esp. streptococcus pneumoniae, H. influenzae and meningococci
  • therefore give Pneumococcus, Hib, menC and flu vaccine before elective splenectomy
  • lifelong penicillin V 500mg twice daily (erythromycin if penicillin allergic)
22
Q

What 3 histological findings are characteristic on blood film following a splenectomy?
-clue: 2 bodies, one shape of cell

A
  • Howell-Jolly Bodies
  • Pappenheimer Bodies
  • Target Cells
23
Q

There is a pentad of symptoms in thrombotic thrombocytopenia purpura (TTP) , name 3 of them:

A
  • microangiopathic haemolytic anaemia
  • thrombocytopenia
  • AKI
  • neuro sx: headache, palsies, seizure, confusion, coma
  • fever
24
Q

What causes thrombotic thrombocytopenia purpura (TTP)

clue: brother

A
  • congenital deficiency or acquired antibodies against ADAMTS13 protease (which normally cleaves multimers of vWF)
  • large vWF multimers causes platelet aggregation and fibrin deposition in small vessels –> a multisystem thrombotic microangiopathy
25
Q

Treatment of thrombotic thrombocytopenia purpura (TTP) requires expert help (haematological emergency)
-but fundamentals of treatment is:

A
  • plasma infusion/exchange to remove antibodies/replace ADAMTS13 and can be life-saving
  • corticosteroids
  • rituximab can be considered in relapse
26
Q

What is seen on a peripheral blood film smear in thrombotic thrombocytopenia purpura (TTP)?
What type of anaemia is it?

A
  • schistocytes (RBCs are sheared by the obstructing platelet aggregations intravascularly)
  • microangiopathic haemolytic normocytic anaemia
27
Q

Haemolytic uraemic syndrome (HUS) presents with what triad?

A
  • microangiopathic haemolytic anaemia hb<100g/L, high LDH, low haptoglobin, RBC fragments on blood film
  • thrombocytopaenia
  • AKI (due to thrombosis of the glomerular capillaries)
28
Q

In children what is Haemolytic uraemic syndrome (HUS) commonly associated with?

A

-haemorrhagic colitis due to Shiga toxin producing E. Coli e.g. 0157:H7 (bloody diarrhoea)

29
Q

typical HUS occurs in children and is related to shiga toxin-producing E. coli, what is atypical HUS caused by? (more common in adults)

A
  • caused by dysregulation/uncontrolled activation of complement
  • can be precipitated by pregnancy
30
Q

How is Haemolytic uraemic syndrome (HUS) diagnosed/what investigations should be done?

A
  • triad of haemolytic anaemia, thrombocytopenia and AKI w haem/protein-uria
  • ?evidence of STEC (shiga-toxin producing E.Coli)
  • C3 and C4 levels, factors H and I and complement mutation screen
31
Q

How is Haemolytic uraemic syndrome (HUS) treated?

A
  • supportive if shiga-toxin E coli related

- if atypical: plasma infusion/exchange, eculizumab (anti-c5)

32
Q

Von Willebrand Factor is a plasma glycoprotein that plays a big role in what? Acts on what receptor when?

A
  • role in clot formation

- GPL1 (glycoprotein

33
Q

vWF is synthesised and stored where?

Its synthesis is regulated by the vW gene which is located on which chromosome?

A
  • endothelial cells of megakaryocytes

- short arm of chromosome 12