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YEAR 3 & 5 CORE CONDITIONS > Haematology 2 > Flashcards

Haematology 2 Flashcards

1
Q

What is multiple myeloma?

A

Malignant plasma cell disorder characterised by uncontrolled proliferation and diffuse infiltration of monoclonal plasma cells in bone marrow

These may also secrete monoclonal Ig and/or Ig fragments eg light chain

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2
Q

Describe why anaemia, neutropenia and thrombocytopenia are features of multiple myeloma

A

Bone marrow is infiltrated leading to a suppression of haematopoiesis

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3
Q

Describe why hypercalcaemia is a feature of multiple myeloma

A

Stromal cells (that adhere to myeloma cells), stimulate the production of RANKL, IL-6 and VEGF (cytokines)

RANKL stimulates osteoclast activity, causing the lytic lesions and hypercalcaemia

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4
Q

Describe the impact of overproduction of monocloncal Igs and light chains in multiple myeloma

A

These are non functioning antibodies, leading to a functional antibody deficiency - this leads to recurrent infections (particularly of the respiratory tract)

Increased serum viscosity leads to hyperviscositiy syndrome - spontaneous bleeding (gums, epistaxis, rectal bleeding), visual disturbances and headaches

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5
Q

What is the criteria used in multiple myeloma?

A

All 3 of following must be present:

  1. Monoclonal plasma cells in bone marrow > 10%
  2. Monoclonal protein in serum or urine (unless it is non-secretory in which case you need high bone marrow plasma cells > 30%)
  3. Evidence of organ damage (CRAB)
    ○ Calcium increased (>11mg/dL)
    ○ Renal insufficiency (creatinine clearance <40mL/min or serum creatinine >2mg/dL)
    ○ Anaemia (Hb <100g/L)
    ○ Bone lesions on MRI
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6
Q

How may multiple myeloma present?

A 
Often asymptomatic
Back pain
Symptoms of hypercalcaemia
B symptoms
Anaemia symptoms
Increased risk of infection (especially respiratory tract) 
Increased risk of petechial bleeding
Foamy urine
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7
Q

Why is foamy urine a feature of multiple myeloma?

A

Bence Jones proteinuria

Free light chains (in 20%)

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8
Q

What investigations are done for multiple myeloma?

A

Serum protein electrophoresis - best initial test
Urine protein electrophoresis - looks for presence of Bence Jones’ protein
Bone marrow biopsy - confirmatory test
Bloods - U&Es (hyercalcaemia and renal insufficiency), FBC (anaemia)
Imaging for bone lesions

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9
Q

What does a blood smear show in multiple myeloma?

A

Rouleux formation = aggregation of erythrocytes looks like a stack of coins

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10
Q

What does serum protein electrophoresis show in multiple myeloma? What tests are requested alongside serum electrophoresis?

A

Monoclonal bands (paraproteins)
or
Monoclonal gammopathy of undetermined significance (MGUS)

Serum immunofixation - confirms type of paraprotein e.g. IgA or IgG

Serum free light chains - increases sensitivity of serum electrophoresis and shows presence of Bence Jones’ protein

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11
Q

What proteins are measured in the blood in multiple myeloma?

A

Elevated total proteins = one of the first signs

Paraprotein (gamma) gap = paraproteins produced by malignant plasma cells increase the difference between total serum protein and normal albumin concentration (there is an increase in non-albumin serum proteins)

Increase in ß2 microglobulin

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12
Q

What imaging can be useful in multiple myeloma and what may it show?

A

1st choice = Whole body low dose CT (WBLD CT)
- Shows osteolysis and osteopenia

X ray skeletal survey - multiple lytic lesions (punched out holes)

FDG/PET scans - areas of active osteolysis

MRI - infiltration and replacement of bone marrow

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13
Q

What is the name for when there is a raised level of monoclonal Ig’s in patient serum but without any accompanying clinical symptoms?

A

Monoclonal gammopathy of undetermined significance (MGUS)

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14
Q

What is the diagnostic criteria of MGUS?

A

Monoclonal Igs <30g/L
<10% monoclonal plasma cells in bone marrow
No organ damage (no CRAB)

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15
Q

What can MGUS develop into? What is the management?

A

Multiple myeloma (1%)

No treatment - monitor M protein levels

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16
Q

What is the management of asymptomatic multiple myeloma? When may this not be appropriate?

A

Asymptomatic - watch and wait

Unless >60% clonal cells, excessive free light chains or more than 1 bone lesion

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17
Q

What is the management of symptomatic multiple myeloma?

A

Hematopoietic stem cell transplantation (HSCT) for young patients with minimal comorbidities

MPT (Melphalan + Prednisolone + Thalidomide) or Lenalidomide + low-dose dexamethasone for those unsuitable for transplant

Bone pain:

  • Bisphosphonates
  • Radiation therapy of osteolytic lesions

Pancytopenia with anaemia and infection risk:

  • Blood transfusions
  • Granulocyte colony stimulating factor (G-CSF)
  • EPO
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18
Q

What occurs in light chain amyloidosis in multiple myeloma and what does this lead to?

A

Light chains accumulate as amyloids

Leads to restrictive cardiomyopathy, renal insufficiency, macroglossia and malabsorption syndrome

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19
Q

What renal disease occurs in multiple myeloma?

A

Myeloma cast nephropathy

Light chains are directly toxic to renal tissue and protein complex (cast) formation in the distal nephron leads to tubular obstruction

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20
Q

20% of myeloma have Bence Jones proteins, what are the other two immunoglobulin classifications?

A 
IgG = 50%
IgA = 25%
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21
Q

What is the most common cause of hypercoagulability in white populations?

A

Factor V Leiden

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22
Q

What is the inheritance pattern of Factor V Leiden?

A

Autosomal dominant

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23
Q

Other than Factor V Leiden, name some inherited thromobophilias (hypercoagulablities)

A 
Protein C deficiency
Protein S deficiency
Antithrombin III deficiency
Hyperhomocysteinemia
Plasminogen deficiency
Sickle cell anaemia
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24
Q

Antithrombin III deficiency is usually inherited (autosomal dominant). What can cause it to be acquired?

A

Liver failure
Renal failure
Nephrotic syndrome = urinary loss of antithrombin

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25
Q

What can lead to acquired thrombophilia?

A 
Pregnancy
Inc age
Smoking
Obesity
Surgery
Immobilisation
Trauma
Malignancy (esp adenocarcinoma)
Antiphospholipid syndrome
Nephrotic syndrome
OCP
HRT
SLE
Heparin induced thrombocytopenia
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26
Q

What is the role of protein C?

A

Activated protein C inactivates factor V in the clotting cascade

This decreases the activation of thrombin (which would turn fibrinogen into fibrin creating a clot)

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27
Q

What is activated protein c resistance? What happens?

A

Factor V Leiden

Factor V does not get deactivated, so activates prothrombin to thrombin, fibrinogen gets turned to fibrin, thus there are an increase in thrombotic events

eg peripheral and cerebral vein thrombosis, recurrent pregnancy loss

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28
Q

What is the role of antithrombin III?

A

Normally binds to and inactivates thrombin and FX = inhibiting coagulation

Deficiency leads to decreased inhibition and elevated thrombin and factor X

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29
Q

What is the mechanism of heparin?

A

Indirectly inhibits the action of thrombin and factor Xa by increasing the activity of antithrombin III (an endogenous anticoagulant)
- Increases the effectiveness of antithrombin by over 1000x, reducing clot formation

Acts on the intrinsic pathway

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30
Q

What does heparin do to aPTT? How is this affected in those with antithrombin III deficiency?

A

Normally heparin increases aPTT

However in antithrombin III deficiency, there is no increase

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31
Q

What is hyperhomocysteinemia?

A

Homocysteine = amino acid produced from breakdown of proteins

Usually due to B12 or folate deficiency

Risk factor for CVD, neurodegenerative disease, NTD

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32
Q

What is the pathophysiology of antiphospholipid syndrome?

A

Acquired antibodies directed against plasma proteins bound to phospholipids

Aggregation of plasma proteins(eg clotting factors) induces venous and arterial clotting

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33
Q

What other conditions are linked with antiphospholipid syndrome?

A

SLE

RA

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34
Q

What complications may someone with antiphospholipid syndrome encounter?

A

DVTs
Portal vein thrombosis
Strokes
Miscarriages - often experience clotting inside the placenta leading to spontaneous abortions

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35
Q

Why is pregnancy a hypercoagulable state?

A

Clotting factors increase
Protein C and S decrease
Venous stasis as uterus enlarges

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36
Q

What risk is more associated with UFH vs LWMH?

A

Heparin induced thrombocytopenia

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37
Q

What is heparin induced thrombocytopenia?

A

Immune mediated adverse drug reaction caused by antibodies that activate platelets in the presence of heparin

Creating a prothrombotic state

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38
Q

What length of coagulation is necessary for a VTE that was

1) Provoked
2) Unprovoked

A

1) Provoked = 3 months

2) Unprovoked = 6 months

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39
Q

What may be considered if recurrent VTE / anticoagulant therapy contraindicated?

A

Inferior vena cava filter

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40
Q

What is thrombocytopenia? What are two broad causes?

A

Platelets < 150

Impaired platelet production in bone marrow

Increased platelet breakdown in periphery

41
Q

Which cells in the bone marrow are responsible for making platelets?

A

Megakaryocytes

Perform thrombopoiesis

42
Q

What can cause impaired platelet production in bone marrow?

A 
Bone marrow failure
Bone marrow suppression (chemo / radiotherapy /drugs)
Congenital thrombocytopenias
Infection
Malignancy
Vit B12 deficiency
Folate deficiency
43
Q

List some congenital thrombocytopenias

A

Wiskott-Aldrich syndrome
Alport syndrome
von Willebrand disease
Bernard-Soulier syndrome

44
Q

List some infectious causes of impaired platelet production in bone marrow

A 
CMV
EBV
Hep C
HIB
Mumps
Rubella
Parvovirus B19
Ricketts
VZV
45
Q

What can cause increased platelet turnover/decreased platelet survival in periphery?

A

Immune thrombocytopenia
DIC
TTP and HUS
Drug induced immune thrombocytopenia e.g. HIT
Preeclampsia
HELLP
Prosthetic valves causing mechanical damage

46
Q

How may thrombocytopenia present?

A

(in increasing severity)

Asymptomatic
Prolonged bleeding
Scattered petecchia
Spontaneous bleeding
Disseminated petechial bleeding in skin and mucosa
Easy bruising
Haem emergency
47
Q

What are petechiae?

A

Nonblanchable, nonpalpable, red, pinpoint macules caused by capillary inflammation and hemorrhage

48
Q

How is immune thrombocytopenic purpura (ITP) diagnosed?

A

Diagnosis of exclusion in isolated thrombocytopenia

49
Q

What is primary vs secondary ITP

A

Primary - idiopathic but may be triggered by infection

Secondary - lymphoma, leukaemia (esp CLL), SLE, HIV, Hep C, drug reactions

50
Q

What is the pathophysiology of ITP?

A

IgG antibodies against glycoprotein on platelets

Platelet-antibody complex removed from circulation by spleen

Decreased platelet count

Bone marrow megakaryocytes and platelet production increases in response

51
Q

ITP is common in which demographic and what onset is it usually?

A

Children - usually acute following infection

Women of childbearing age - insidious onset or incidental finding (>12 months)

52
Q

What is the management of children with ITP?

A

If no bleeding or only bruising / petechiae = observation regardless of platelet count

If severe bleeding = glucocorticoids or IV Ig

53
Q

What is the management of adults with ITP?

A

1st line - glucocortoids
or Iv Ig

2nd line - splenectomy

54
Q

How do glucocorticoids help ITP?

A

Glucocorticoids suppress antibody production and/or stop platelet breakdown by inhibiting phagocytosis

55
Q

What happens to the number of megakaryocytes in reduced bone marrow platelet production vs increased platelet turnover

A

Reduced production = reduced number of megakaryocytes

Increased turnover = increased number of megakaryocytes

56
Q

What is pancytopenia?

A

A decrease in number of all cell lines in blood

i.e RBC, WBC, platelets

57
Q

Pneumonic for causes of pancytopenia

A

PANCYTO

Paroxysmal nocturnal hemoglobinuria (PNH)
Aplastic anaemia
Neoplasms / near neoplasms
Consumption
Vitamin deficiencies
Toxins / drugs / radiotherapy
Overwhelming infections
58
Q

What is PNH?

A

Disorder of stem cells that leads to an increased sensitivity to complement mediated cell lysis

59
Q

How can PNH present?

A

Coombs test negative intravascular hemolysis (ie not autoimmune haemolysis)

Hypercoaguable state

+/- bone marrow aplasia

60
Q

Why is aplastic anaemia a misnomer?

A

It is a disorder of stem cells thus affects all cell lines (not just RBC)

61
Q

What are some causes of aplastic anaemia?

A

Many idiopathic

Fanconi’s anaemia
Drugs and toxins
Infections
Immune disorders

62
Q

Which drugs are associated with aplastic anaemia?

A 
Chemo
Chloramphenicol
Sulfa drugs
NSAIDs
Anti epileptics
63
Q

What infections are most commonly associated with aplastic anaemia?

A

Parvovirus B19 most commonly

Also Hep, HIV, CMV, EBV

64
Q

Which neoplasms may cause pancytopenia?

A

Leukaemia
Mets

Near neoplasms = myelodysplastic syndrome

65
Q

What is the management of pancytopenia?

A

Increase each cell line

RBC transfusions
Platelet transfusions
Granulocyte colony stimulating factor
Abx for patients with fever in setting of neutropenia

66
Q

What do lymphoid precursor cells produce?

A

B Lymphocytes
T lymphocytes
Natural killer cells

67
Q

What do myeloid precursor cells produce?

A

Erythrocytes
Granulocytes (basophil, eosinophil, neutrophil)
Megakaryocytes

68
Q

What does a left shift in blood mean?

A

Increase in immature progenitor cells

Usually due to infection eg increase in band neutrophils (?)

69
Q

Compare ‘-cytosis’ vs ‘-emia’

A

A reactive increase of a cell line ends in “-cytosis” eg leukocytosis

A neoplastic increase is “emia” eg leukemia

70
Q

What happens to aPPT in antiphospholipid syndrome?

A

Paradoxical rise in aPTT (strange as you would think short aPTT as a clotting vibe)

Lupus antibodies react with phospholipids involved in coagulation cascade - ie they get used up so can take longer to clot when doing aPTT

Normal PT

71
Q

Compare pancytopenia to aplastic anaemia, what investigations would you do?

A

Pancyotpenia = generalised blood finding

Aplastic anaemia = distince definable disease

Do bone marrow biopsy (would be “empty” in aplastic anaemia)

Check for splenomegly

72
Q

What is hypersplenism?

A

Increases spleen activity meaning cells are removed from blood faster - can result in a decrease of one or multiple cell lines

This leads to a reactive bone marrow hyperplasia

73
Q

Splenomegaly can be caused by 3 broad causes. What are these?

A

1) Increased activity of spleen
2) Decreased venous drainage
3) Splenic infilatration

74
Q

What can cause increased activity of the spleen?

A

1) Increased degradation of defective cells
- Eg haemolytic anaemias such as thalassaemia, spherocytosis, sickle cell
- Eg Polycythemia vera

2) Increased immune response to infection

3) Defective immune response
- Vasculitis
- Connective tissue disease
- RA
- SLE
- Sarcoidoisis

4) Compensatory extramedullary haemaotpoiesis within the spleen due to bone marrow deficiency
- Myelofibrosis
- Lymphoma

75
Q

What can lead to decreased venous drainage which can lead to splenomegaly?

A

Portal hypertension

  • Liver cirrhosis
  • Obstruction of portal, hepatic or splenic vein
  • Schistosomiasis
76
Q

Which condition is linked to Philadelphia chromosome? What number and what gene?

A

CML

Philadelphia Chr t(9;22) resulting in the formation of a BCR-ABL fusion gene

Promotes unregulated profileration of myeloid precursor cells

77
Q

What are the three phases of CML?

A

Chronic phase
Acclerated phase
Blast crisis

78
Q

Describe the chronic phase of CML - duration and symptoms

A 
Can persist for 10 yrs
Often subclinical
Symptomatic includes:
- Weight loss
- Fever
- Night sweats
- Fatigue
- Splenomegaly (LUQ pain)

(not lymphadenopathy)

79
Q

Which of AML or CML is characterised by recurrent infection during early stages? Why?

A

AML = recurrent infections

CML = granulocytes are still fully functional

80
Q

Describe the accelerated phase of CML

A

Erythrocytopenia = anaemia
Neutropenia = infection and fever
Extreme pleocytosis (rapid increase in number of malignant cells)
- Infarctions eg splenic and MI, retinal vein occlusion
- Leukaemia priapism
- Terminal phase = myelofibrosis
MASSIVE splenomegaly

81
Q

Describe the blast stage of CML

A

Resembles acute leukaemia

Rapid progression of bone marrow failure
- Pancytopenia
- Bone pain
Severe malaise

82
Q

What is seen in a blood smear of CML

A 
Leucocytosis
Basophilia
Eosinophilia
Blasts = indicate accelerated phase
Thrombocytosis
83
Q

What is the management of CML?

A

Tyrosine kinase inhibitors (Imatinib) - first-line

Allogenic stem cell transplant if unsuccessful or for young patients as a curative therapy

84
Q

How can CLL be differentiated from CML on presentation?

A

Lymphadenopathy present in CLL not CML

85
Q

How else does CLL present?

A 
B symptoms
Painless LN
Hepatomegaly
Splenomegaly
Recurrent infections
Anaemia symptoms
Thrombocytopenia symtpms
86
Q

What is seen on a peipheral smear of CLL?

A

Smudge cells

Crushed Little Lymphocytes (CLL)

87
Q

What is the management of CLL?

A

CLL = low grade malignancy, it has slow rate of cell division and disease progression

Treatment if not often necessary or unlikely to improve survival time
- Only curative tratment is stem cell transplantation

88
Q

What are the two types of haematopoietic stem cell transplantation?

A

Autologous = removal and storage of patients own cells which are retransfused back after high dose chemo

Allogenous = transplant of stem cells from sibling or donor

89
Q

When are autologous stem cell transplants indicated?

A

High-dose chemotherapy would destroy the bone marrow and therefore cannot be used to treat neoplastic disease without subsequent bone marrow transplantation
- So use to allow higher doses to be used eg soft tissue sarcome

Multiple myeloma
Lymphoma

90
Q

What are advantages of autologous stem cell transplants?

A

Low risk of graft vs host disease
Low risk late post transplant infection
Low risk of graft rejection

91
Q

What are disadvantages of autologous stem cell transplants?

A

High risk of early post transplant infection due to prolonged neutrophil infection (you’ve taken away their own bone marrow)

No graft vs tumour effect (when donour t cells attack malignant cells)

92
Q

What are some indications for allogenous stem cell transplantation?

A

To replace abnormal but non malignant cells in the lymphohamatopoietic system eg:
Immunodeficiency
Aplastic anaemia
Thalassaemia

Also leukaemia

93
Q

What are some advantages for allogenous stem cell transplantation?

A

Graft vs tumour effect

Low risk early post transplant infection

94
Q

What are some disadvantages for allogenous stem cell transplantation?

A

Risk of graft vs host disease
Late post transplant infection
Inc risk of infection
Can cause chromosomal abnormalities in blood / bone marrow due to discrepancy between genotype and phenotype

95
Q

Agranulocytosis vs neutropenia

A

Agranulocytosis = low WCC (mot commonly neutrophils)

Neutropenia = low neutrophils

96
Q

Which drugs are associated with agranulocytosis?

A

Clozapine
Carbamazepine
Valproate
Carbimazole + other anti thyroids

97
Q

What is intravascular vs extravascular haemolysis?

A

Intravascular = RBC within vessel

Extravascular = phagocytosis of RBC

98
Q

What can be measured to check for intravascular haemolysis? Is it low or high and why?

A

Haptoglobin

It is low bc it is a protein which binds free Hb - if it is low then there is free Hb (as RBC have been destroyed) so this binds the haptoglobin

99
Q

What can be given to increase neutrophil count in pt who are neutropenic?

A

Granulocyte colony stimulating factors

eg Filgrastim
Perfilgrastim

YEAR 3 & 5 CORE CONDITIONS (30 decks)

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