Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BPT Flashcards > Haematology > Flashcards

Haematology Flashcards

1
Q

Favourable prognostic factors of AML

A

t(8;21)
t(15;17) - APML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Unfavourable prognostic factors of AML

A

FLT3-ITD
Translocations i.e. t(6;9), t(9;22)
Complex pattern of aberrations
Karyotype abnormalities (trisomy 8, monosomy 5 or 7/deletions of chromosome 5 or 7)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Targeted therapies for FLT-3 mutated disease

A

TKIs - midostaurin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Pathognomonic abnormality of APML

A

t(15;17); PML-RARa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Treatment for APML

A

Differentiation therapy -
Arsenic trioxide
All-trans retinoic acid (ATRA)

Induces maturation of malignant cells into WBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Treatment toxicities of ATRA therapy and clinical features

A

Differentiation syndrome
- Acute respiratory distress
- Fevers
- Shock
- Pleural/pericardial effusions
- Treatment with dexamethasone

QTc syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Definition of myelodysplastic syndrome

A

Haematological cancers causing qualitative and quantitative defects in haematopoisis, resulting in malfunction of pleuripotent stem cells leading to hypercellularity and dysplasia of the bone marrow –> results in cytopenia of one or more cell lines (thrombocytopenia, erythrocytopenia, leukocytopenia).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Aetiology of MDS

A
  • Primary MDS (idiopathic), more common in elderly
  • Secondary MDS (caused by exogenous bone marrow damage) –> treatment-related following cytostatic therapy (alkylating agents, topoisomerase II inhibitors, azathioprine, etc.),
    benzene and other organic solvents, radiation damage,
    paroxysmal nocturnal hemoglobinuria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Treatment choice for del(5q)

A

Lenalidomide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Treatment for MDS

A

Dependent for severity, but largely supportive treatment i.e. blood/platelet transfusions, prophylactic antimicrobials, growth factors

Only curative treatment is allogenic bone marrow transplant for high risk patients

Lenalidomide for MDS with isolated del(5q)

Azacitadine for intermediate risk disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Luspartercept mechanism of action

A

SMAD2/3 signalling inhibitor, promoting late-stage differentiation and correcting erythropoiesis

Used in MDS where there is increased SMAD2/3 signalling, causing ineffective erythropoiesis

Effective in patients with ring sideroblasts (SF3B1 mutation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Chromosome and gene associated with CML

A

Philadelphia chromosome, associated with gene fusion of BCR-ABL1

Caused by t(9;22)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Clinical hallmark of CML

A

Uncontrolled production of granulocytes, primarily neutrophils, but could be basophils and eosinophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Phases of CML

A
  • Chronic CML (CP-CML) - can persist to up to 10 years and often subclinical
  • Accelerated CML (AP-CML) - anaemia, signs of neutropenia, splenomegaly
    PB myeloblasts 15-29%
    PB myeloblasts and promyelocytes combined >/ 30%
    PB basophils >/ 20%
    Platelets </ 100
  • Blast CML (BP-CML) - progression to myeloid blast crisis (i.e. AML) or lymphoid blast crisis (i.e. ALL)
    >/ 30% myeloblasts in blood, bone marrow or both
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

CML treatment

A

Tyrosine kinase inhibitors
- First generation: Imatinib
- Second generation: Dasatinib, nilotinib
- Third generation: Ponatinib (Required if 315I mutation)

Hydroxyurea for patients with extreme leukocytosis or symptomatic splenomegaly

Interferon-alpha is an option for pregnant patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Imatinib side effects

A

Diarrhoea, fluid retention, muscle pains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Dasatinib side effects

A

Pleural effusions, pulmonary HTN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Nilotinib

A

High BSLs, accelerated vascular disease, pancreatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Ponatinib

A

High risk of CVD events

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

MOA of asciminib

A

ABL1 inhibitor
Approved for CML resistant to 2 or more TKI agents including patients with T315I mutation

Side effects – pancreatitis, fatigue, nausea, headache

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Clinical hallmark of polycythemia vera

A

Persistent erythyrocytosis, with increased haematocrit - resulting in hyperviscosity and increased risk of thrombosis/poor oxygenation

Can also have leukocytosis and thrombocytosis

Other signs - splenomegaly, aquagenic pruritis, thrombosis, vasomotor symptoms (e.g. erythromelalgia)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Diagnostic criteria for PCV

A

Major critiera
- Hb > 165 or Hct > 49% (men) or 48% (women)
- BM biopsy - hypercellularity for age
- Presence of JAK2 or JAK2 exon 12 mutation

Minor criteria
- Subnormal serum erythropoietin level

3 major or 2 major and 1 minor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Treatment of PCV

A

Regular phlebotomy and aspirin

Cytoreductive therapy (hydroxyurea or peginterferon) if high risk PCR (age> 60 yrs, previous thrombotic event) or low risk PCV not responding to phlebotomy and aspirin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Target Hct for PCV

A

<0.45

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Clinical hallmark of essential thrombocytosis

A

Persistent thrombocytosis with bone marrow changes of megakaryocyte proliferation

Splenomegaly, thrombosis, vasomotor symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Diagnostic criteria of ET

A

Major criteria
- Thrombocytosis
- BM biopsy demonstrating megakaryocyte proliferation
- Exclusion of other differentials including CML, PCV, PMF, MDS
- Demonstration of genetic mutation (JAK2, CALR, MPL)

Minor criteria
- Demonstration of another clonal marker or no other identifiable cause of thrombocytosis found i.e. infection, inflammation, IDA

4 major or 3 major and 1 minor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Treatment of ET

A

Low risk patients - aspirin or observation only
High risk patients - aspirin + cytoreductive therapies

Cytoreductive therapies -
1st line: hydroxyurea, recombinant IFN alpha
2nd line: phosphodiesterase inhibitor (anagrelide), busulfan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Clinical hallmark of primary myelofibrosis

A

Disorder of megakaryocytes, with prominent cytokine release causing marrow fibrosis, extramedullary hematopoiesis, and splenomegaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Treatment of primary myelofibrosis

A

Monitor for low risk patients
Symptomatic splenomegaly - ruxolitinib (JAK inhibitor), hydroxyurea
Symptomatic cytopenias - transfusions
Allogenic transplant is curative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Mutations in MPNs

A

JAK2, CALR2 exon 9, MPL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Features of mastocytosis

A

Abnormal mast cell proliferation and accumulation in tissues

Associated with mutations in c-Kit gene and elevated serum tryptase levels

Results in high histamine levels, leading to:
Pruritus, flushing, abdominal pain, diarrhea, hypotension
Gastric ulcers (due to increased gastric acid secretion)

Subtypes - cutaneous and systemic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Subtypes of mastocytosis

A

Cutaneous - skin manifestations i.e. urticaria

Systemic - symptoms of mast cell mediator release i.e. multisystem disorder, anaphylaxis without stimulus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Features of chronic myelomonocytic leukaemia

A

Overlap between MPN and MDS

Persistent monocytosis and features of dysplasia

Higher risk of transformation to AML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Clinical hallmark of CLL

A

Defined by >5x 10^9/L monoclonal cells, manifesting as lymphocytic leukocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Pathophysiology of CLL

A

Acquired mutations in hematopoietic stem cells → increased proliferation of leukemic B cells with impaired maturation and differentiation in the bone marrow, resulting in:
- Suppression of the proliferation of normal blood cells
- Immunosuppression (Hypogammaglobulinemia,
Granulocytopenia)
- Thrombocytopenia
- Anemia
- Infiltration of the lymph nodes, liver, and spleen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Indications for treatment in CLL

A
  • Significant cytopenias
  • Bulky (symptomatic) lymph nodes or rapidly growing
  • B symptoms
  • Rapid lymphocyte doubling time
  • Significant fatigue due to CLL
  • Transformation to another histology
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Definition of Richter’s transformation

A

CLL to DLBCL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Poor prognostic factors of CLL

A

17p deletion
TP53 mutation
IGHV UNmutated status
11q deletion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Treatment for CLL

A

First line treatment
- BTK inhibitor - ibrutinib, acalabrutinib
- BCL2 inhibitor- venetoclax
- PI3K inhibitor - idelalisib

Adjunctive therapies
- CD20 inhibitor - rituximab, obinutuzumab
- CD52 inhibitor - alemtuzumab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

MOA of rituximab

A

CD20 inhibitor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

MOA of alemtuzumab

A

CD52 inhibitor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Ibrutinib MOA/side effects

A

BTK inhibitor
- drastically spikes lymphocyte count, then slowly brings it down

Atrial fibrillation
Mild bruising - due to platelet dysfunction and impaired clot formation
Mild GI side effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Venetoclax MOA/Side effects

A

BCL2 inhibitor

Very high risk of TLS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Definition of MGUS

A

Paraprotein < 30g/L
BM plasma cells < 10%
No CRAB or SLiM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Definition of smouldering myeloma

A

No CRAB or SLiM
Paraprotien > 30g/L and/or BM plasma cells 10-59%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Definition of active myeloma

A

BM plasma cells > 10%
Myeloma defining event

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

CRAB criteria

A

HyperCalcaemia
Renal failure
Anaemia
Bone lesions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

SLiM criteria

A

Plasma cells> 60% (Sixty) in marrow
Light chain ration > 100
Multiple focal lesions on MRI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Risk of MGUS progression to myeloma

A

1% each year

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Subtypes of myeloma

A

IgA and IgG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Pathophysiology of myeloma

A
  • Neoplastic proliferation of plasma cells
    Bone marrow infiltration by malignant plasma cells → suppression of hematopoiesis → leukopenia, thrombocytopenia, anemia
    Cell proliferation → pro-osteoclastogenic factors (e.g., TNF-α, IL-1, RANK-L) → osteolytic lesions → hypercalcemia
  • Overproduction of monoclonal immunoglobulin and/or light chains → dysproteinemia (a state of pathologically increased synthesis of immunoglobulins and/or their subunits) → kidney damage (e.g., myeloma cast nephropathy) and/or paraprotein tissue deposition (may cause amyloidosis) [3][4]
    Nonfunctioning antibodies → functional antibody deficiency
    ↑ Serum viscosity → hyperviscosity syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

MM treatment for transplant eligible patients

A
  1. Induction therapy (bortezomib, lenalidomide, dexamehtasone) - 3-6 cycles
  2. Stem cell transplant (high dose chemotherapy with stem cell reserve)
  3. Maintenance lenalidomide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

MM treatment for NON-transplant eligible patients

A
  • Bortezomib, cyclophosphamide, dexamethasone
  • Lenalidomide, dexamethasone
  • Lenalidomide, bortezomib, dexamethasone

Relapsed disease
- Daratumumab, lenalidomide
- Daratumumab, bortezomib, melphalan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Lenalidomide MOA/side effects

A

Immunomodulator (-lidomide)

Diarrhoea, muscle cramps, VTE risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Thalidomide MOA/side effects

A

Immunomodulator (-lidomide)

Neuropathy, constipation, fatigue, VTE risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Bortezomib MOA/side effects

A

Proteasome inhibitor (-zomib)

Neuropathy, thrombocytopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Carfilzomib MOA/side effects

A

Proteasome inhibitor (-zomib)

Idiosyncratic cardiac events, renal failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Daratumumab MOA/Side effects

A

anti-CD38 antibody

URTI, neutropenia

Leads to non-specific positive antibody screen on routine transfusion testing

Pts should have extended phenotype performed prior to first infusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Vincristine SE

A

Peripheral neuropathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Doxorubicin SE

A

Cardiomyopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Follicular lymphoma treatment

A

First line
- Obinutuzumab-bendamustine or obinutuzumab-CHOP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Follicular lymphoma genetic abnormality

A

Translocation t(14;18), which involves the heavy-chain Ig (chromosome 14) and Bcl-2 gene (chromosome 18) → overexpression of Bcl-2 → dysregulation of apoptosis (normally inhibited by Bcl-2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

B cell lymphomas

A

Indolent:
- Follicular lymphoma
- Hairy cell lymphoma
- Marginal cell lymphoma
- Waldenstrom
- SLL

Aggressive:
- DLBCL
- Mantle cell lymphoma
- Burkitt
- Precursor B-cell lymphoblastic lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Hairy cell leukaemia pathology

A

Presence of mature lymphocytes with “hairy” border on blood film

Absolute monocytopenia, cytopenias and splenomegaly

High incidence of BRAFV600E mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Waldenstrom macroglobulinaemia definition

A

Lymphoplasmacytic lymphoma with associated IgM paraprotein

66
Q

Genetic mutation in WM

A

MYD88 mutation

67
Q

WM treatment and indications

A

Treatment for symptomatic patients i.e. anaemia, hyperviscocity

Anti-CD20 antibody (rituximab)
BTK inhibitors (venetoclax)
Chemotherapy - purine nucleoside analogs (fludarabine and cladribine), alkylating agents (e.g., cyclophosphamide)

Hyperviscocitiy syndrome (due to overproduction of IgM) - plasmapharesis

68
Q

Marginal zone lymphoma features

A
  • Associated with autoimmune diseases (e.g., Sjogren syndrome, Hashimoto thyroiditis)

Types
- Extranodal MZL: gastric MALT lymphoma (most common) and nongastric MALT lymphoma (e.g., thyroid, salivary gland)
- Nodal MZL (or monocytoid B-cell lymphoma)
- Splenic MZL

Gastric MALT lymphoma: associated with translocation t(11;18)(q21;q21) and H. pylori infection

69
Q

Mantle Cell lymphoma features

A
  • Translocation t(11;14) involving cyclin D1 (chromosome 11) and heavy-chain Ig (chromosome 14) → increased levels of cyclin D1 → promotes the transition of cells to S phase
    CD5+
  • Spreads rapidly; most patients are diagnosed with advanced disease (stage IV)
70
Q

Burkitt leukaemia/lymphoma features

A

Extremely aggressive
Associated with translocation in myc and immunodeficiency
High risk of CNS involvement

Translocation t(8;14) in 75% of cases: reciprocal translocation involving the c-myc gene (chromosome 8) and heavy-chain Ig locus (chromosome 14) → overactivation of c-myc proto-oncogene → activation of transcription

Types:
- Sporadic (located in abdomen or pelvis)
- Endemic (associated with EBV, located in maxillary and mandibular bones)

Starry sky pattern

71
Q

Brentuximab MOA/SE

A

Anti-CD30 antibody drug conjugate

peripheral neuropathy

72
Q

Hairy cell leukaemia treatment

A

1st line - cladribine or pentostatin

73
Q

Intrinsic pathway factors and measurement

A

APTT

Factors 8, 9, 11, 12

74
Q

Extrinsic pathway factors and measurement

A

PT

Factors 7, tissue factor

75
Q

Common pathway factors and measurement

A

APTT and PT

Factors 2, 5, 10

76
Q

Cell based model of coagulation phases

A

Initiation phase
- exposure of TF, factor 7 and initial platelet activation

Amplication phase
- Production of thrombin (2a)
- Activates factor 5, 8, and 9
- Accelerates 10a production and further thrombin generation

Propagation phase
- Conversion of prothrombin (2) to thrombin (2a)
- Allows conversion of fibrinogen to fibrin, and activation of factor 13

77
Q

Fibrinolysis initiators

A

Plasminogen activators
- tPA and urokinase

Cleared by liver

78
Q

Fibrinolysis regulators

A

Prevents excessive fibrinolysis

  • Plasminogen activator inhibitors (PAIs)
    PAI-1: inactivates tPA and urokinase. Released from endothelium and activated platelets.
    PAI-2: from placenta
  • Plasmin inhibitor
    a2-antiplasmin: free or clot bound
  • TAFI
    Thrombin activatable fibrinolysis inhibitor
    Removes lysine residues from fibrin
79
Q

MOA of transexamic acid

A

Antifibrinolytic
Competitively inhibits binding of plasmin and plasminogen to fibrin by blocking lysine binding sites of plasminogen

Renally cleared

80
Q

PT measurement and abnormalities

A

Extrinsic and common pathway

Vitamin K deficiency
Warfarin +/- rivaroxaban
Liver disease
Factor 7 deficiency/inhibitor
Common pathway if APTT also abnormal

81
Q

APTT measurement and abnormalities

A

Intrinsic and common pathway

Factor 8, 9, 11 or 12 deficiency or inhibitors
LAC
Common pathway if PT also abnormal
UFH +/- dabigatran

82
Q

Fibrinogen abnormalities

A

Decreased
- DIC
- Liver disease
- Congenital abnormality

Increased
- Thrombosis
- Infection
- Inflammation
- Pregnancy

83
Q

Thrombin time abnormalities

A

Increased
- Thrombin problem (heparin, dabigatran, amyloid)
- Fibrinogen/fibrin problem (paraprotein)

84
Q

Anti-Xa measurement and abnormalities

A

Measures extent an anticoagulant inhibits factor Xa function

UFH, LMWH, rivaroxaban, apixaban

85
Q

Mixing test interpretation

A

Correction - factor deficiency

No correction - factor inhibitor

Immediate: lupus inhibitor, factor 9 inhibitor
Delayed: factor 8 inhibitor

86
Q

MOA of warfarin

A

Oral vitamin K antagonist

Prevents vitamin-dependent y carboxylation of glutamate residues on factor 2, 7, 9, 10
Depletes protein C and S

87
Q

Warfarin reversal

A

Urgent: prothrombin complex concentrate, FFP
Semi-urgent: Vitamin K
Elective: Withhold doses +/- bridging heparin

88
Q

Heparin MOA and monitoring

A

Potentiates anti 10a +/- anti 2a effect on antithrombin III

APTT for UFH
Anti-Xa for enoxaparin or UFH

89
Q

Heparin reversal

A

Protamine sulfate for UFH (limited utility for LMWH)
Stop infusion

90
Q

Dabigatran MOA

A

Direct thrombin inhibitors
Inhibits circulating and clot bound thrombin

91
Q

Apixaban and rivaroxaban MOA

A

Direct factor Xa inhibitor

92
Q

Dabigatran reversal

A

Idarucizumab (Praxbind)
Monoclonal antibody fragment
Binds dabigatran with higher affinity than thrombin
Binds free and thrombin-bound dabigatran and neutralises its activity

Approved for lifethreatening bleeding and emergency procedures

93
Q

Apixaban/rivaroxaban reversal

A

Andexanet alfa
Recombinant modified factor Xa decoy
Binds and neutralises anticoagulants effects of direct and indirect Xa inhibitors

94
Q

Factors that alter D-dimer level

A

Trauma, inflammation, age, pregnancy

95
Q

APLS criteria

A

Revised Sapporo/Sydney criteria
>/ 1 clinical and >/ 1 lab criteria

Clinical criteria
- Vascular thrombosis (arterial, venous or small vessel)
- Pregnancy morbidity (unexplained foetal death, premature birth or >/ 3 consecutive spontaneous miscarriages)

Lab criteria (presence on >/ 2 occasions at least 12 weeks apart)
- Lupus anticoagulant
- Anticardiolipin antibody
- Anti beta-2 glycoprotein-I antibody of IgG and/or IgM

96
Q

Warfarin anticoagulation indications

A

Mechanical heart valve
Renal impairment
APLS
Breast feeding

97
Q

LMWH anticoagulation indications

A

Malignancy (though accumulating evidence for DOACs)
Pregnancy

98
Q

Indications for IVC filter

A

Consider in pts with acute BTE and contraindication to anticoagulation i.e. active bleeding

99
Q

Therapeutic targets and MOA of clopidogrel

A

Thienopyridine inhibitor (including prasugrel)

Targets substance ADP which acts on receptor P2Y1 and P2Y32

Causes platelet shape change and aggregation

100
Q

Ticagrelor MOA

A

Non-thienopyridine inhibitor

Targets substance ADP which acts on receptor P2Y1 and P2Y32

Causes platelet shape change and aggregation

101
Q

Examples of fibrinogen inhibitors

A

Abciximab, eptifibatide, tirofiban

Acts on GPIIb/IIIa receptor

102
Q

ITP causes

A

Idiopathic
Secondary causes
- Viruses i.e. HIV, HCV
- Malignancy, particularly CLL
- Antigen stimulation i.e. H. pylori
- AI conditions i.e. APLS, SLE

103
Q

ITP pathophysiology

A

Antiplatelet antibodies (mostly IgG directed against, e.g., GpIIb/IIIa, GpIb/IX) bind to surface proteins on platelets → splenic and liver sequestration → ↓ platelet count → bone marrow megakaryocytes and platelet production increase in response (in most cases)

104
Q

DDx for ITP

A

Peripheral destruction
- TTP, DIC, HITS
Marrow causes
- MDS
Splenic sequestration
Artefactual - platelet clumping
Gestational thrombocytopenia - more likely in second/third trimesters

105
Q

ITP Management

A

Treatment of underlying cause
Avoid antiplatelets/NSAIDs - drugs that impair platelet function

Prednisone
IVIg (use whilst awaiting effects of prednisone)
Splenectomy (6-80% long term remission) + asplenic prophylaxis

Thrombopoietin receptor agonists
- Romiplostim 1-2mcg/kg/weekly SC
- Eltrombopag 50mg daily PO
- Avatrombopag

106
Q

TTP causes

A

Primary
- Congenital ADAMTS13 deficiency (Upshaw-Schulman syndrome)

Secondary
- Antibodies against ADAMTS13 due to drugs (quinidine, gemcitabine), malignancy, infection, HIV, pregnancy

107
Q

TTP pathophysiology

A

ADAMTS13 deficiency → decrease in vWF breakdown → accumulation of vWF on endothelial cell surfaces → platelet adhesion and microthrombosis → MAHA

108
Q

TTP clinical pentad

A

MAHA
Fever
Renal impairment
Thrombocytopenia
Neurological impairment

Do not wait for pentad to occur

109
Q

TTP DDx

A

HUS - Shiga toxin producing E Coli
atypical HUS - Complement dysregulation → treat with eculuzimab
DIC
ITP
HITS

110
Q

TTP management

A

Urgent plasma exchange
FFP/cryodeplete plasma
Steroids

Other specialist therapies
- Caplacizumab - immunoglobulin fragment targeting A1 domain of vWF - preventing interaction between vWF and platelet glycoprotein Ib-Ix-V receptor

111
Q

MOA of caplacizumab

A

Antibody targeting A1 domain of vWF - prevents interaction between glycoprotein Ib-IX-V receptor and vWF

112
Q

MOA of eculizumab and indications

A

Anti-C5 humanised chimeric monoclonal antibody
Targets terminal component of complement cascade (reduces haemolysis)
Vulnerability to infection by encapsulated organisms

Uses:
- Atypical HUS
- PNH

113
Q

Causes for reduced Hb

A

Reduced production
- Iron deficiency
- Vitamin B12 deficiency
- Renal failure
- BM disorder

Increased destruction
- Haemolysis
- Thalassaemia

114
Q

Causes for increased Hb

A

Reactive
- Respiratory (hypoxia)
- Renal disease
- Increase EPO (tumour, illicit)
- High affinity Hb

Clonal
- Polycythaemia vera

115
Q

Causes for microcytic anaemia

A

Iron deficiency
Thalassaemia
Anaemia of chronic disease
Myelodysplasia - usually macrocytic
Sideroblastic anaemia
Hyperthyroidism
Heavy metal poisoning

116
Q

Blood film features of IDA

A

Microcytic, hypochromic red cells
Increased central pallor
Reduced haemoglobinisation

117
Q

Mechanisms of anaemia of chronic disease

A

Altered/abnormal iron homeostasis
Reduced red cell production by bone marrow
Blunted response to erythropoietin
Shortened red cell survival

118
Q

Iron studies for IDA

A

Iron reduced
Transferrin increased
Tsats reduced
Ferritin reduced

119
Q

Iron studies for anaemia of chronic disease

A

Iron reduced
Transferrin reduced to normal
Tsats reduced
Ferritin normal to increased

120
Q

Blood film features of B12/folate deficiency

A

Macrocytes, oral macrocytes, megaloblastic anaemia

121
Q

Differential diagnosis of macrocytic anaemia

A

Megaloblastic erythropoiesis
- B12/folate deficiency
- Drugs: anti-folate drugs (MTX, pentamidine, trimethoprim), DNA synthesis (azathioprine, hydroxyurea, zidovudine, phenytoin)

Reticulocytosis
- Haemolysis
- Bleeding

Others
- BM pathology (MDS, myeloma, aplastic anaemia)
- Liver disease
- Copper deficiency, arsenic poisoning
- Down syndrome

122
Q

B12 deficiency causes

A
  • Pernicious anaemia - autoimmune destruction of gastric mucosa/parietal cells
  • Nutrition
  • Intestinal pathology (CD, ileal resection, tapeworm infection)
  • Gastrectomy
  • Congenital deficiency
  • TCII deficiency
  • Nitrous oxide poisoning
  • Congenital pernicious anaemia (lack of IF)
123
Q

Diagnosis of pernicious anaemia

A

IF antibodies (very specific, 50% sensitive)
Parietal cell antibodies (sensitive but non-specific)

124
Q

Clinical findings of B12 deficiency

A

Insidious onset, macrocytic anaemia
Glossitis, angular stomatitis
Neural tube defects
Subacute combined degeneration of spinal cord

125
Q

Blood films of B12 deficiency

A

Macrocytic anaemia
Hypersegmented neutrophils
Oral macrocytes
Low reticulocyte count

126
Q

Drugs that can cause megaloblastic anaemia

A

Metabolic
- Azathioprine
- Mycophenolate
- MTX
- Gemcitabine
- Hydroxyurea
- Leflunomide

Reduced absorption
- Metformin
- PPI
- Alcohol
- Phenytoin
- Isoniazid

127
Q

Blood test results of haemolysis

A

Increased reticulocytes
- immature RBC containing RNA polychromasia on film
Increased LDH
- increased cell turnover
Decreased haptoglobin
- glycoprotein from lifer, binds free Hb
Increased unconjugated bilirubin

128
Q

Causes of haemolysis

A

Intravascular
- Fragmentation
- PNH
- PCH

Extravascular
- Immune mediated
- RBC membrane
- RBC enzymes
- Metabolic defects
- Bacterial and parasitic infections

129
Q

Findings of intravascular haemolysis

A

Very reduced haptoglobin
Positive urinary haemosiderin (if chronic)

130
Q

Findings of extravascular haemolysis

A

Reduced haptoglobin
Negative urinary haemosiderin

131
Q

Blood film finding of haemolysis

A

Red cell fragmentation - schistocyte, fragments, Helmut cells

132
Q

Causes for microangiopathic haemolytic anaemia (MAHA)

A

TTP
HUS
Pre-eclampsia, HELLP, malignant HTN, renal allograft rejection
Atypical HUS

133
Q

Causes for red blood cell fragmentation

A
  • MAHA
  • DIC
  • Mechanical haemolytic anaemia - prosthetic heart valves, severe cardiac valvular disease
  • Vascular malformations - hemangiomas
  • Direct damage by heat, venoms, toxins etc.
  • Malignant HTN
134
Q

Blood film findings of hereditary spherocytosis

A

Polychromasia, prominent spherocytes

135
Q

Clinical findings of hereditary spherocytosis

A

Jaundice
Cholelithiasis
Splenomegaly

136
Q

Diagnostic findings of hereditary spherocytosis

A

Family history
Film - polychromasia, prominent spherocytes
FBC - increased MCHC, RDW, reticulocytes
DAT - NEGATIVE
Flow cytometry - eosin-5-maleimide (EMA) binding

137
Q

Blood film findings of G6PD deficiency

A

Bite cells and blister cells

138
Q

Pyruvate kinase deficiency

A

“Prickle” cell, nucleated red cell

139
Q

Features of G6PD deficiency

A

Hexose-monophosphate pathway
Acute haemolytic crisis
Susceptibility to oxidative stress
X linked

140
Q

Features of pyruvate kinase pathway

A

Glycolytic pathway
Chronic haemolysis
Reduced ATP formation –> RBC rigidity
Autosomal recessive

141
Q

Reactions G6PD are involved in

A

Production of NADPH for protection against oxidative stress
Oxidation of glucose-6-phosphate

141
Q

Survival advantage of G6PD deficiency

A

Against P falciparum infections

142
Q

Features of G6PD deficiency

A

Precipitant induced haemolytic crisis - rapid development
Blood film - bite cells, blister cells
Severe disease resulting in chronic haemolysis

143
Q

Definition of haemoglobinopathy

A

Synthesis of abnormal haemoglobin

144
Q

Definition of thalassaemia

A

Reduced rate of synthesis of normal haemoglobins

145
Q

Normal haemoglobin structures

A

Haemoglobin A (a2B2) - main haemoglobin in adults (97%)

Haemoglobin A2 (α2δ2) - minor haemoglobin (2-3%)

Haemoglobin F (a2y2) - primary form in neonates, minor haemoglobin in adults (<1%)

146
Q

Abnormality in a-thalassaemia

A

Reduced a-globin production (reduced Hb A, A2, F)

147
Q

Types of a-thalassaemia

A

a0 thal: deletion or inactivation of both alleles on single chromosome
a+ thal: one allele inactivated on same chromosome

148
Q

Abnormality in B-thalssaemia

A

Reduced B-globin production (reduced HbA)

Genetic abnormality - deletions

149
Q

Types of B-thalassaemia

A

B0: Abnormal gene is not expressed

B+: Reduced expression of abnormal gene

Genetic abnormality - small deletions/mutations (>200)

150
Q

Definition of HbH disease

A

(–/-a)
Chronic haemolysis, splenomegaly, HbH inclusions

151
Q

FBC findings of HbH disease

A

Reduced Hb
Very reduced MCH/MCV
Many HbH cells

152
Q

Definition of Hydrops foetalis

A

(–/–)

Incompatible with extra-uterine life

153
Q

B-thalassaemia trait/minor pathophysiology

A

Results in reduced B-globin synthesis, therefore reducing HbA (a2B2)and compensatory increase in HbA2 (α2δ2)
Results in haemolysis and ineffective erythropoiesis

154
Q

Features of B-thalassaemia trait/minor

A

Clinically asymptomatic/mild anaemia
FBC - reduced MCV (<72) and MCH (<27), poikilocytosis, basophilic stippling, target cells
HPLC - increased HbA2, increased HbF

155
Q

Pathophysiology of B-thalassamia major

A

Homozygous or compound heterozygotes for B-thalassaemia with absent of severe deficiency of B-globin production

156
Q

Features of B-thalassaemia major

A

Severe anaemia
Developmental delay
Skeletal abnormalities
Iron overload
Marked anisopoikilocytosis, stippling, NRBCs

Elevated HbA2 and HbF
Reduced or absent HbA

157
Q

Management of B-thalassaemia major

A

Transfusion support
Supportive care - endocrine failure, bone disease, risk of VTE
Stem cell transplant
Iron chelation therapy - desferrioxamine, deferiprone, exjade

158
Q

Sickle cell haemoglobin pathophysiology

A

Synthesis of abnormal haemoglobin
Due to GAG to GTG; B globin gene
Substitutes valine for glutamic acid (HbS)
HbS polymerises into long fibres on deoxygenation

159
Q

Sickle cell disease Hb

A

Hb S/S, C/S, B/S

160
Q

Management of sickle cell disease

A

Hydroxyurea - foetal haemoglobin induction
Transfusion
Monitor HbS levels
Risk of infections (due to hyposplenism)

Voxeleter (HbS polymerisation inhibitor) - phase 3 clinical trials showed increased Hb and reduced haemolysis

BPT Flashcards (32 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions