Brainscape's Knowledge GenomeTM

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


See full index

FRACP Exam > Haematology > Flashcards

Haematology Flashcards

1
Q

Acquired thrombocytopaenia

A

liver disease: portal HTN with splenic sequestration, decrease thrombopoeitin

uraemia: platelet dysfunction

DM: platelet dysfunction (increased activity with thromboses)

drug induced Ab/BM suppression

  • usually drug induced Ab destroy platelet but also BM suppression

- common: quinidine, penicillin, digoxin, anti-epileptics, heparin

drug preventing aggregation:

  • aspirin: irreversible COX inhibition
  • NSAIDs: reversible COX inhibition
  • clopidogrel: prevents platelet aggregation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Alpha thalassemia

A

genetics: 4 genes on chromosome 16

pathophysiology: decreased alpha increases other chains

  • decreased HbA, HbA2, HbF
  • b4 (HbH)
  • g4 (Barts Hb)
  • overtime Bart’s Hb is replaced with HbH

clinical (see chart)

treatment: folate, transfusion, iron chelation, splenectomy

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

Anaemia

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

Anaemia chronic disease

A

pathogenesis:

  • decreased lifespan RBCs and relative BM failure
  • decrease iron availability as trapped in macrophages

diagnosis:

  • low serum iron, high ferritin, normal binding capacity
  • normocytic, normochromic anaemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Anti-phospholipid antibodies

A

types: anti-cardiolipin antibodies, lupus anticoagulant

diagnosis: prolonged APTT, does not correct on mixing

  • DOES correct with adding phospholipid

clinical: risk of clotting, not bleeding

  • children post viral illness, older with AI (SLE, ITP, Addison’s, RF)
  • must be present >3 months to increase risk of clotting
  • arterial/venous thrombosis, recurrent miscarriage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Aplastic anaemia

A

definition: pancytopaenia with hypocellular/hypoplastic bone marrow (replaced by fat)

causes

acquired :

  • idiopathic 80%
  • other: drugs, radiation, virus, PNH, pregnancy

hereditary: Fanconi (most common), Schwachmann Diamond, Dyskeratosis Congenita

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

Autoimmune thrombocytopaenia

A

pathophysiology: maternal Ab against both maternal/foetal platelets

  • associated materal ITP/SLE

clinical: low maternal platelets

  • neonatal thrombocytopaenia (20-50 with nadir days 2-5)
  • neonatal petechiae/bruising/bleeding

management: monitor, transfusion, IVIG, methylpred, materanl IVIG/pred

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

Bernard Soulier

aka. hemorrhagiparous thrombocytic dystrophy

A

prevalence: 1/1,000,000

genetic: AR

pathogenesis: deficiency of glycoprotein Ib (Gb1b) the receptor for vWF

diagnosis: thrombocytopaenia, increased megakaryocytes, decreased GpIb/V/IX

clinical: bleeding gyms, bruising, bleeding with minimal trauma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Bernard Soulier syndrome

A

pathogenesis: absence of vWF receptor (GpIb complex) on platelet membrane

diagnosis: thrombocytopaenia, large platelets, prolonged bleeding time >20mins

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

Blackfan-diamond anaemia

A

definition: congenital pure red cell aplasia

pathophysiology: ineffective erythropoiesis

genetics: AD

clinical: presents infancy

  • progressive normochromic/macroocytic anaemia, reticulocytopaenia
  • normal cellularity BM

associations:

congenital malformations (50%)

  • craniofacial, eye, neck, cardiac, thumb, GUT

growth retardation 30%

treatment:

  • corticosteroids (40% steroid dependent)
  • blood transfusions (40% transfusion dependent)

prognosis: 20% go into remission

complications: hemosiderosis requiring Fe chelation

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

Cell morphology

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

Clotting factors half lives

A

Factor VII 2-4 hours

Factor VIII 12 hours

Factor IX 24 hours

Factor X 30 hours

Prothrombin 3.5 days

Fibrinogen 2-4 days

Factor XIII 5-7 days

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

Clotting times

A

reptilase time: conversion of fibrinogen to fibrin (heparin fx)

bleeding time: interaction platelet with BV wall (normal<3 mins)

D-dimer: breakdown products of fibrinogen

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

Coagulation cascade

A

Primary hemostasis: initial immediate platelet plug

Secondary haemostasis: via intrinsic/extrinsic cascade with fibrin

Intrinsic (Contact): Factors 8, 9, 11, 12

Extrinsic (Tissue Factor): Factor 7

Common pathway: Factors 2, 5, 10, Fibrinogen

Cofactors:

  • calcium: for every step except 11/12
  • phospholipids: create factor III
  • vitamin K: produce 2, 7, 9, 10, protein S, protein C, protein Z

Regulators:

  • protein S: cofactor for protein C
  • protein C: inactivates 5a and 8a
  • antithrombin III: inactivates thrombin and Xa
  • heparin (mast cells): accelerates antithrombin 1000x
  • tissue factor pathway inhibitor (TFPI): limits activation of X
  • plasmin: digests fibrin clots
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Coagulation cascade

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

Coagulation tests

A

PT/INR: extrinsic/common pathway

  • normal: PT < 18 secs, INR <2 secs
  • disorders: vit K def, factor VII def, warfarin, DIC

APTT: intrinsic/common pathway

  • normal: <70 secs
  • disorders: factor 8, 9, 11, 12 deficiencies (<40%), herparin, lupus anticoag
  • mixing studies: corrects if factor deficiency

PT/APTT prolonged

  • disorders: prothrombin, V, X, fibrinogen, liver disease, vit K def, herparin + warfarin, DIC

Fibrinogen:

  • normal: <17 secs
  • low: liver, DIC, fibrinogen def, thrombolytic therapy
  • high: acute phase reactant, malignancy, OCP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Cold agglutinin haemolytic anaemia

A

pathogenesis: intravascular haemolysis with anaemia/hemoglobinuria due to high titer of cold antibodies (IgM)

clinical: anaemia, haemoglobinuria, dark urine, less splenomegally than warm

film: RBC agglutination into irregular clumps

treatment: avoid cold, cytotoxic agents, IVIG, plasmaphoresis (only lasts 5 days)

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

Concomitant alpha and beta thalassemia

A

presence of alpha trait lessens severity of beta thalassemia

  • reduction in alpha globin synthesis reduces the burder of alpha globin inclusions without affection haemoglobin made
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Congenital abnormalities of platelet function

A

Bernard-Soulier:

  • AR defect in glycoprotein receptor on platelet for binding vWF
  • severe thrombocytopaenia, giant platelets, poor aggregation, bleeding

Glanzmann thrombasthaenia

  • AR defect in fibrinogen receptor causing platelet dysfunction preventing aggregation
  • normal platelet count
  • mucocutaneous bleeding

Grey platelet syndrome

  • absence of platelet alpha granules causing them to look grey
  • defective platelet activation/aggregation

Wiskott-Aldrich

  • XLR immunodeficiency, thrombocytopaenia, eczema
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Congenital Amegakaryocytic Thrombocytopaenia

A

genetic: rare, AR

pathophysiology: myeloproliferative leukaemia virus oncogene that encodes thrombopoitein and is needed for platelet production

clinical: neonatal thrombocytopaenia, bleeding into skin/mucosa/GI

  • pancytopaenia later in childhood

treatment: BMT, limit transfusion

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

Congenital thrombocytoapaenia

A

Congenital amegakaryocytic thrombocytopaenia (CAMV)

  • megakaryocytes absent in BM due to receptor defect
  • pancytopaenia develops
  • treatmentL BMT

Thrombocytopaenia-Absent Radius (TAR) syndrome

  • thrombocytopaenia, hypereosinophilia, absent radius, bilat DDH, limb shortening
  • associated cow’s milk intolerance 50%
  • remits in 1st year of life
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Diagnosis/Clinical features of haemophilia

A

diagnosis: prolonged APTT (intrinsic pathway)

  • corrects on mixing studies unless high inhibitor titres

clinical: usually presents <1yr

  • 2% intracranial haemorrhage
  • 30% bleeding post circumcision
  • haemarthroses: ankle 1st
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Diamond-Blackfan Anaemia

A

definition: congenital erythroid aplasia

clinical: present in infancy

  • progressive normochronic/macrocytic anaemia
  • reticulocytopaenia
  • normal BM/WCC/platelets
  • 50% assoc congenital abnormalieis
  • increased risk of malignancies: AML, myelodysplastic sx, solid tumours

diagnostic criteria:

  • age<1
  • macrocytic anemia
  • reticulocytopaenia
  • normal marrow

treatment: steroids, bloods transfusion, HCT

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

DIC

A

mechanism: widespread consumption of clotting factors, platelets and anticoagulation proteins producing

  • widespread fibrin clots with ischaemia and necrosis
  • haemorrhagic state
  • microangiopathic haemolytic anaemia

trigger: any systemic disease associated with hypoxia, acidosis, tisse necrosis, shock

diagnosis: increased INR/APTT/TT, decrease platelets/Hb/fibrinogen

association: overtbleeding

treatment: cause, correct acidosis/hypoxia, blood products (FFP)

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

Disorder of fibrinogen

A

source: made in liver

function: formation of fibrin clot, supports platelet aggregation

  • fibrin clot is template for thrombin or fibrinolysis

diagnosis: abnormal APTT/INR as in final p/w

  • corrects with mixing

types:

_dysfibrinogenaemia:_abnormal fibrinogen molecules

  • congenital or acquired (liver disease)

afibrinogaemia/hypofibrinogaemia

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

Dyskeratosis Congenita

A

genetics (3 mechanisms): X linked, AR, AD

  • multiple genes

clinical: BM failure with ectodermal abnormalities

  • hyperpigmented rash over face/neck/trunk
  • nail dystrophy
  • mucosal leukoplakia
  • increased risk of malignancies

diagnosis: genetic testing, telomere length analysis

management: androgens, BMT

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

Factor half lives

A

Factor VII: 2-4 hours

Factor VIII: 12 hours

Factor IX: 24 hours

Factor I/II: 2-4 days

Factor XIII: 5 days

**Factors involved in clot formation have longer half lives

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

Factor V deficiency

(parahaemophilia)

A

genetics: AR

clinical: mild bleeding, menorrhagia

treatment: FFP

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

Factor V Leiden mutation

A

incidence:

  • 6% heterozygotes: 5x risk thrombus
  • homozygotes: 100x risk thrombus
  • increased risk with OCP

pathophysiology: mutation in factor V that prevents it being inhibited by activated protein C

30
Q

Factor X deficiency

A

genetics: rare, autosomal

associations: amyloidosis due to absorption of factor X on amyloid protein

31
Q

Factor XII deficiency

A

genetic: AR, rare

diagnosis: APTT prolonged, PT normal

clinical: delayed separation of umbilical cord, delayed bleeding of umbilical stump, ICH, poor wound healing

32
Q

Factor XIII deficiency

F13D

A

function: cross-links fibrin clot

pathophysiology: unstable clot

clinical: delayed bruise/bleed, poor wound healing

treatment: FFP/cryoprecipitate, recombinant factor XIII

33
Q

Fanconi anaemia

A

incidence: heterozygote 1/300, consanguinity 10%, assoc affected siblings

genetic: AR, 15 different FA genes

  • FA-A 65% chromosome 16
  • FA-C/FA-G 10% each

pathophysiology: protein involved in DNA repair

clinical:

  • diagnosis 6-9 years

congenital malformations 60-70%

  • short stature 50%
  • hyperpigmented spots/cafe au lait
  • abnormality of thumbs: bifid/hypoplastic
  • radial hypoplasia/absent radius
  • facies: microcephaly, small eyes, epicanthic folds, abnormal ears
  • hypogonadism
  • DD
  • hypospadias, cryptorchidism, phimosis

associations: malignancies (myelodysplastic syndrome, AML, SCC, Wilm’s tumour), endocrine/opthalmological/renal/GI/CVS issues

diagnosis: BM failure in 1st decade

  • thrombocytopaenia, anaemia (macrocytic, increased HbF), leukopaenia, increased AFP
  • chromosome breakage studies (add mitomycin C/diepoxybutane)

management: BMT, androgens (improve anaemia>thrombocytopaenia>neutropaenia) in 50%, GCSF, transfusions

prognosis by 40yrs:

  • BM failure 90%, haem malignancy 30%, non haem malignancy 30%, mortality 80%
34
Q

G6PD

A

G6PD :1st enzyme in hexose monophosphate pathway (5% RBC metabolism)

  • reduces NADP to NADPH for reduction of glutathione
  • absence of reduced glutathione causes accumulation of oxidants and intracellular precipitation of Hb

genetics: XLR

  • female heterozygotes protected against malaria
  • 3 mutations: A (africa 15%), B (Med/Asian 5-40%), D (China 5%)

clinical: neonatal onset jaundice OR acute haemolytic episode

  • triggers: fava beans, napthalene, medications, illness

diagnosis:

  • heinz bodies seen under blue stain: removed 1-4 days
  • haemolysis (bite cells)
  • direct enzyme activity: <10% normal

management: avoid precipitants, supportive during episodes

35
Q

Glanzmann Thrombasthenia

A

prevalence: RARE

genetic: AR or AI

pathogenesis: platelets contain defective GpIIb/IIIa which is the receptor for fibrinogen preventing crosslinking of platelets

clinical: bruising, epistaxis, GI bleed, post-op bleeding

diagnosis: bleeding time significantly prolonged

36
Q

Haemolytic anaemia

  • categories-
A

INTRINSIC

  • enzyme defects: G6PD, pyruvate kinase def
  • haemoglobinopathies: sickle cell, thalassemias
  • membrane defects: hereditary spherocytosis, elliptocytosis

EXTRINSIC

  • autoimmune haemolytic anaemias: warm reactive/cold reactive
  • liver disease: cirrhosis, hypersplenism
  • oxidant agents: nitrates, dapsone, aniline dyes
  • microangiopathies: HUS, DIC, artificial heart valves, Kasabach Merritt
  • paroxysmal cold haemoglobinuria
  • paroxysmal nocturnal haemoglobinuria
37
Q

Haemophilia

A

cause: reduced factor VIII/IX causing delay in thrombin and fibrin clot

genetics: X-linked recessive, spontaneous mutations 1/3

both types identical clinical picture:

haemophilia A (85%): 1/5000, most reduced levels of protein (5-10% dysfunctional protein)

  • most common mutation internal inversion within the FVIII gene

haemophilia B (10-15%): 1/25,000, 50% reduced protein, 50% dysfunctional protein

severity: based on % of factor in the plasma

  • <1% severe with spontaneous bleeding
  • 1-5% moderate with bleeding in minor trauma
  • >5% mild bleeding in significant trauma

(normal haemostatic level for both factors in 30%)

38
Q

Haemophilia management

A

MANAGEMENT

F__actor replac__ements with bleeds: treat early and enough

  • factor levels 50% for mild/mod bleeds, 100% for life threatening
  • treat for 14 days in major bleeds

Factor VIII

  • half life 6 hours for first dose
  • repeat doses 12 hourly if necessary
  • 1u/kg raises FVIII by 2%

Prophylactic factor replacement: 2-3 days to maintain 1-2%

  • severe haemophilia: prevents joint deformities

DDAVP

  • mild haem A: causes endogenous FVIII to be released from endo stores

Supportive

  • avoid contact sports
  • blood products: cryo (FVIII, fibrinogen), FFP (FIX)
  • screen for hepB, hepC, HIV

Complications

  • arthropathy: bleed into joint space with inflammatory changes to synovium and increased bleeding risk
  • inhibitors: 30% in Haem A, need to desensitize if high
  • failed desensitization: FVIIa or activated prothrombin complex to bypass inhibitor
39
Q

Hepcidin

A

function: inhibits Fe absorption in small intestine/placenta and decreases release from macrophages

release: acute phase reactant (induced by IL-6)

  • increases with inflammation, malignancy, infection
  • decreases Fe in inflammation

diagnosis: assays not available

40
Q

Heinz Bodies

A

pathogenesis: precipitated Hb

causes: G6PD

41
Q

Hereditary elliptocytosis

A

genetics: RARE

clinical: similar to spherocytosis

42
Q

Hereditary spherocytosis

A

incidence: 1/5000

genetics: autosomal dominant

pathophysiology: abnormality of spectrin OR ankyrin (components of cytoskeleton for RBC shape)

  • spherocytes less deformable and destroyed by the spleen

clinical: variable severity

  • haemolytic disease of newborn, medullary expansion of bones, splenomegally, bilirubin gallstones, risk aplastia crisis

diagnosis: high retics/bilirubin, low haptoglobin

film: small hyperchromic spherocytes

management: splenectomy (Hb <100, retics >10%) age 5-6 yrs, folate

43
Q

Transfusion risk

A

Haemolysis

  • acute: ABO incompatibility
  • delayed

Infection: bacterial > viral

bacteria: skin (staph/strep), storage (yersinia)
- rRBC out of fridge max 4 hours
- platelets MOST risk: stored at room temp 5 days

viral:

  • HIV 1/9 million
  • HCV 1/3 million
  • HBV 1/1 million
  • HTLV 1/1 million

In Australia testing for HIV/HBV/HCV/HTLV/syphillus

44
Q

Howell Jolly-Bodies

A

pathogenesis: contain nuclear remnants

causes:

  • post spleenectomy
  • megaloblastic anaemia
  • iron deficiency anaemia
45
Q

Idiopathic Thrombocytopaenic Purpura

ITP

A

incidence: 3/100,000 per year

pathophysiology: acquired transient immune mediated thrombocytopaenia

  • autoAb (IgG) bind platelet mem Ag esp glycoprotein IIb/IIIa complex
  • preceding history of infection

clinical: platelets

  • acute: platelets return to normal within 6 months
  • chronic: 15% of acute >6months, older children, assoc atypical presentations, assoc underlying AI disorder
  • petechiae/purpura/bruising
  • mucosal/conjunctival/retinal haemorrhage
  • ICH (0.1-1%, platelets

treatment if NOT bleeding: conservation

treatment if bleeding:

  • IVIG (binds Fc prolonging survival, increase 24hrs, 85% respond),
  • steroids: improve vasc integrity, decreased Ab affinity, most respond
  • transfusion: half life can be 10mins, only life threatening bleed
46
Q

Iron deficiency Anaemia

A

incidence: most common nutritional deficiency

  • most common in toddlers: 12-36 mths 9% deficient, 3% anaemia

pathophysiology: 75% Fe bound to Hb/myoglobin

  • hard to maintain stores rapid growth in infancy
  • 30% iron from diet

etiology: insufficient intake, decreased absorption, blood loss

clinical: pallor, irritability, tachycardia, cardiomegally, decreased exercise tolerance, pica, splenomegally (15%), brittle nails, blue sclera, angular stomatitis

associations: increased breath holding, long term neurodev. impact, increased thrombosis

diagnosis: low total Fe/ferritin/transferrin, high TIBC/RDW

film: eliptogenic RBCs

BM: hypercellular, erythroid hyperplasia

management: 6mg/kg elemental iron/day 45mins before meals

outcome: increased Hb by 10 in 4 weeks

47
Q

Iron Physiology

A

source:

  • iron absorbed duodenum
  • released RBC/monocytes/macrophages

location:

  • haemoglobin, myoglobin, ferritin, haemosiderin, enzyme bound
48
Q

Lupus anticoagulant

A

definition: antibody against phospholipid and other factors

effect: prolongs APTT and does not correct on mixing studies

risks: paradoxical risk of CLOTTING if presents > 3 months

etiology:

  • post viral in children
  • autoimmune in adults
49
Q

Methaemoglobinaemia

A

etiology: congenital or acquired

pathophysiology:

  • Fe2+ bound to Hb and Fe3+ when released
  • Fe3+ binds water to produce MetHb
  • cytochrome 5b breaks down MetHb
  • metHb occurs when NADH-cytochrome 5b reductase deficient

OR

- toxic substances: medications (NO, metoclopramide, sulfonamides), medical condictions (GI infection, SS pain crisis), pesticides

clinical:

  • poor oxygen carrying capacity
  • cyanosis >15%, death >70% metHb
50
Q

Neonatal alloimmune thrombocytopaenic purpura

A

incidence: 1/5000

pathophysiology: maternal Ab against foetal plts that contain paternal Ags (HPA)

  • most non-HPA1a mother and HPA1a foetus: 75% anti-HPA1a, 16% Anti-HPA5b, 4% Anti-HPA15b
  • form in 1st trimester causing foetal/neonatal thrombocytopaenia

clinical:

  • petechiae/purpura in days
  • higher risk of haemorrhage than ITP: ICH 14%
  • platelets fall in days and rise by 4 weeks

diagnosis: low platelets, normal coags, platelet typing neonate/mother

treatment: IVIG to mother from 2nd trimester onwards, monitor plt count via umbi line sampling, LSCS, platelet transfusion, neonate IVIG, methylpred

prognosis: subsequent pregnancies more severe

51
Q

Normal haemoglobin

A

structure: tetramer with 2 pairs of globin chains

distribution:

  • HbF (α2γ2):
  • HbA2 (α2d2):
  • HbA (α2β2): >95%
52
Q

Paroxysmal cold haemoglobinuria

A

incidence: RARE, assoc cold antibody anti-P

pathophysiology: intravascular haemolysis assoc with low temps

  • post viral in children
  • does NOT cause agglutination like IgM positive does

clinical: similar to warmAb, 7-10 days post febrile illness and persists for 6-12 weeks

  • haemoglobinuria mins-hrs post cold exposure

diagnosis: jaundice, reticulocytosis, haemosiderinuria, bilirubinaemia, reduced haptoglobin/complement, DAT positive

53
Q

Paroxysmal nocturnal haemoglobinuria

A

pathophysiology: RBC membrane defect in GPI anchor causing increased sensitivity to complement

clinical: marrow failure 60%, haemolytic anaemia, haemoglobinuria (nocturnal/morning), hypercoagulable state, decreased haematopoesis

associations: AML, myelodysplasia

diagnosis: flow cytometry to detect absent GPI

management: steroids for acute haemolysis, anticoagulants for thrombosis, Fe therapy, splenectomy NOT useful, androgens/EPO/GH, BMT

prognosis: 80% 5yr survival, mortality due to thombosis/pancytopaenia

54
Q

Protein C/S deficiency

A

incidence: 1%

clinical:

  • homozygous protein C def: purpura fulminans in neonate

pathophysiology:

type 1: quantitative

type 2: qualitative

treatment: FFP

  • once >1 month: warfarin + FFP/protein C
55
Q

Prothrombin (FII) deficiency

A

diagnosis: prolonged PT/PTT

clinical: mucocutaneous, traumatic bleeding

treatment: FFP, prothrombin complex concentrates

56
Q

Prothrombin gene mutation

A

incidence: 2%

genetics: mutation 20210

pathophysiology: increased prothrombin synthesis

clinical:

  • 3x risk of thrombis
  • increased risk with OCP/pregnancy
57
Q

Pyruvate kinase deficiency

A

genetics: autosomal recessive

pathophysiology: decreased activity pyruvate kinase depleting RBCs of ATP

  • secondary elevation of 2,3-DPG

clinical: mild to severe anaemia with pallor, icterus, splenomegally

film: polychromatophilic/spiculated erythrocytes

treatment: exchange transfusion, transfusions, splenectomy (not curative)

58
Q

Sickle cell disease

A

incidence: 1/2500

pathophysiology:

  • single base pair change at the β globin gene
  • poorly soluble when not carrying O2 and susceptible to polymerization resulting in elongated shape and sickling
  • sickle cells increase blood viscosity (Hct>30%) and adherence

clinical:

  • S: stroke (20% by 18), swelling, splenic sequestration, asplenic
  • I: infections, infarction: bone infection SALMONELLA
  • C: cardiac, chest, chronic haemolysis, crises
  • K: kidney problems
  • L: liver disease, lung problems
  • E: erections, eye problems

diagnosis: anaemia with retics, high SBR/LDH, low haptoglobin

  • DNA testing, Hb electrophoresis

film: sickled cells, Howell-Jolly bodies, target cells

mangement: prophylactic penicillin/fluvax, folic acid, hydroxyurea (decreases HbS), chronic transfusion (HbS

59
Q

Sideroblastic anaemia

A

pathophysiology: defect in synthesis of haem within RBC precursors

  • decreased d-ALA or ferrochelatase and decreased incorporation of Fe into porphyrin ring
  • causes accumulation of Fe in mitochondria of nucleated RBCs (sideroblasts)

causes:

  • hereditary: XLR (presents late childhood, splenomegally), AR, Pearson syndrome (refractory, pancreatic dysfunction)
  • acquired: pure sideroblastic anaemia, malignancy, chronic inflammation, drugs (EtOH, isoniaxid, chloramphenicol, lead), nutrition (low copper/folic acid, high zinc), hypothermia, uremia, hyperthyroidism

diagnosis: high serum iron/ferritin, low transferrin

film: micro/macrocytic RBCs, high RDW, basophilic stippling, low retic count

BM: ring sideroblasts

treatment: cause, supportive, transfusions, vit B6

60
Q

Spherocytes

A

definition: sphere shaped and not biconcave red blood cells

causes: hereditary spherocytosis, AIHA

61
Q

Target cells

A

pathogenesis: increased SA to volume

causes:

  • post spleenectomy/non-functioning spleen
  • liver diisease
  • thalassaemias
62
Q

Thalassemia

A

genetics: 2 genes on chromosome 11

  • >200 mutations producing decreased production

types:

  • β thalassaemia major: complete absence of β globin (β0/β0)
  • β thalassaemia minor: partial absence of β globin (β+/β) or (β0/β)

clinical (see chart)

  • increased HbF and HbA2

treatment:

  • folate, blood transfusions 4-6 weeks (Hb>100), hep B vaccine, iron chelation (from 4yrs), splenectomy, BMT
63
Q

Thrombocytopaenia

A

increased destruction:

  • immune: autoimmune, alloimmune, drug induced
  • peripheral consumption: hypersplenism, infection, DIC, Kasabach-Merritt syndrome, drug toxicity
  • procedure related

decreased production:

  • congenital thrombocytopaenias
  • maternal PET
  • infections: viral, bacterial, fungal
  • drug toxicity
  • trisomies 13, 18, 21, Turner’s syndrome

impaired function:

  • uraemia
  • congenital forms
64
Q

Thrombocytopaenia and Absent Radii

TAR

A

genetic: 1q21.1

clinical: absent radius and thrombocytopaenia

65
Q

Thrombotic thrombocytopaenic pupura

A

incidence: 0.3/100,000, 10-40yrs, F>M

risk factors: pregnancy, OCP, metastases, HIV, vasculitis, SLE, drugs

pathophysiology: excess ultra high molecular weight vWF from deficient activity of ADAMTS13

  • ADAMTS13: metalloproteinase in plasma cleaves UHMvWF secreted by endo cells to yield multimers
  • accumulation UHMvWF causes platelet adhesion/aggregation

forms:

acquired: inhibitory Ab blocks ADAMST13 activity
hereditary: AR recessive deficiency ADAMTS13 (Upshaw-Schulman)

PENTAD:

  • microangiopathic haemolytic anaemia: schistocytes
  • thrombocytopaenia
  • neurological: plt<30, diffuse/focal symptoms
  • acute renal failure
  • fever

diagnosis: usually clinical, also hyaline thrombi in BV wall, DAT neg

film: schistocytes, polychromasia, nucleared RBCs

management: remove UHMvWF, decreased ADAMST13 inhibitor, increased ADAMST13, plasma exchange, FFP, steroids

complications: haemorrhage, RF, stroke, coma, CHF, death

prognosis: estimated degree anaemia/thrombocytopaenia/LDH

  • mortality >90% if untreated
  • 1/3 of patients relapse
66
Q

Transient Erythroblastopaenia of Childhood

(TEC)

A

definition: transient/temporary red cell aplasia

pathophysiology: decreased RBC production

clinical: self limited anaemia in previously healthy child

  • reticulocytopaenia
  • 2 month course with remission
67
Q

Transient erythroblastopaenia of childhood

TEC

A

pathophysiology: transient cessation of erythropoiesis

incidence: children 1-4 years, M>F

etiology:?viral serum inhibitors against RBCs, ?inherited response to environmental stimuli

clinical: anaemia 6-8g/dL, mild neutropaenia

  • lasts 1-2 months before complete recovery

treatment: DO NOT respond to steroids

68
Q

Vitamin K deficiency bleeding

  • haemorrhagic disease of the newborn-
A
  • consider child < 9 months with bruising/bleeding

vitamin K: group of compounds with a common, structure, fat soluble

  • K1: diet fortified foods, green leafy veg, legumes
  • K2: intestinal bacteria
  • limited stores/half life
  • deficiency after 4 days no intake

vitamin K dep factors: 2, 7, 9, 10, protein C, protein S

pathophysiology:

  • Vit K dep factors low at birth and drop further 48-72 hrs w/o vit K
  • returns to normal levels 7-10 days

deficiency: vit K low in breast milk and neonates absent bacterial flora

clinical:

early onset (<24hr): rare and life threatening

  • bleed: cranial, GI, umbilicus
  • cause: maternal phenytoin, warfarin, rifampicin, isoniazid, inherited coagulopathy
  • prevention: vit K birth

classic disease (2-7 days): 2% if vit K not given

  • bleed: GI, umbi, ENT, IC, cutaneous, injection, circumcision
  • cause: Vit K def, BF
  • prevention: vit K birth

late onset (1-6 months): primary disease

  • bleed: IC**, cutaneous, GI, ENT, injection
  • cause: cholestatis, malabsorption
  • treat: high dose vit K

diagnosis: prolonged INR/APTT, low 2, 7, 9,10

management: IV vit K (onset 4-6 hrs), FFP/whole blood

69
Q

Von Willebrand Disease

A

incidence: most common bleeding disorder, 1-2% population

genetics: AD, chromosome 12

levels: vary age, stress

pathophysiology: vWF large glycoprotein made by megakaryocyte/endo cells

function as adhesive protein:

  • platelets: vWF binds subendothelium at site of damage, changes confirmation to allow platelet binding through glycoprotein receptor causing activation
  • factor VIII: vWF carrier protein for FVIII

clinical:

type 1/2: mucocutaenous bleeding childhood/adolescence

  • bruising, epistaxis, menorrhagia, postop haemorrhage

type 3: present earlier with more severe bleeding

classification:

  • type 1: quantitatively reduced but not absent (80%)
  • type 2: qualitatively abnormal
  • type 3: quantitatively absent (severe)

diagnosis:

  • coags (normal OR abnormal): increase APTT (FVIII)/bleeding
  • vWF Ag levels/structure
  • vWF activity (ristocetin cofactor activity)
  • decreased FVIII activity

treatment:

  • avoid aspirin, NSAIDS, alcohol, antihistamines
  • desmopressin: release vWF from endothelium (type 1)
  • replacement therapy: plasma derived vWF)

complications: bleeding is rare

70
Q

Warfarin

A

mechanism: inhibits clotting factors II, VII, IX, X, protein C/S

half life: 40 hours

increased effect (drugs induce cP450)

  • carbamazepine, phenytoin, phenobarb, rifampicin, OCP

decreased effect (drugs INHIBIT cP450)

  • isoniazid, fluconazole, CCB, erythromycin
71
Q

Warm reactive haemolytic anaemia

A

pathophysiology: circulating Ab against own RBCs

  • etiology unknown ?viral ?drug induced

clinically 2 patterns:

primary AIHA: fulminant presentation

  • acute onset pallor, jaundice, hemoglobinura preceded by RTI
  • splenomegally
  • responsive to CS with low mortality and complete remission

secondary AIHI: related to SLE/lymphoma

  • chronic disease course with significant mortality

diagnosis: Hb<60, spherocytosis/polychromasia, reticulocytosis, nucleated RBCs, leukocytosis, Ig Ab positive, DAT positive

treatment: transfusion, prednisone, splenectomy, immunosuppression

72
Q

Haemolytic Anaemia

A

FRACP Exam (23 decks)

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