Haematology Flashcards
What are the features of warm AIHA?
37 degree IgG extravascular haemolytic \+ve Coombs test Blood film - spherocytes
What are the causes of warm AIHA?
Mainly primary idiopathic Lymphoma CLL SLE Methyldopa
What are the features of cold AIHA?
<37 degrees IgM intravascular haemolytic \+ve Coombs Often with Raynauds
Causes cold AIHA?
primary idiopathic lymphoma infections EBV mycoplasma
Management warm AIHA?
Steroids
splenectomy
Immunosuppression
Management cold AIHA?
Treat underlying condition
avoid the cold
chlorambucil
Causes of inherited haemolytic anaemia?
membrane - hereditary spherocytosis
cytoplasm - G6PD deficiency
haemoglobin - SCD or thalassaemia
Causes of acquired haemolytic anaemia?
immune mediated:
cold/warm
alloimmune
non immune mediated: infection (malaria) paroxysmal nocturnal haemoglobunuria prosthetic heart valves MAHA - adenocarcinoma - HUS - TTP spherocytosis -ve coombs test
what is the HUS triad?
MAHA
thrombocytopenia
AKI
(e.coli toxin 0157)
how does adenocarcinoma cause haemolytic anaemia?
releases granules into circulation
pro-coagulant and active coag cascade
platelet activation, fibrin deposition, degranulation
red cell fragmentation due to low grade DIC
bleeding (low platelet and coagulation factor deficiency)
TTP pentad?
MAHA thrombocytopenia AKI neurological impairment fever
what causes TTP?
Deficiency in VWF cleaving protease -> high VWF -> cheese wire in blood vessels
Autoimmune: anti-glycoprotein 2b/3a antibody
Mx TTP?
plasma exchange
NOT STEROIDS
Findings on TLS Ix?
hyperkalaemia
hyperphosphataemia
hypocalcaemia
+ clinical features
lab >=2 of: within 7 days chemo or 3 days before Uric acid >475 umol/l or >25% increase K>6 mmol/l or 25% increase PO4 >1.125 or 25% increase Ca <1.75 or 25% decrease
clinical:
>=1.5x ULN creatinine
cardiac arrhythmia or sudden death
seizure
Mx TLS?
prophylaxis:
high risk: IV allopurinol or IV rasburicase
low risk: PO allopurinol
Indications for packed RBC transfusion?
no ACS - maintain >70 x10^9/L
ACS - maintain >80
Indications for platelet transfusion?
pre-procedure - maintain >50 x10^9
50-75 x 10^9 if high risk of bleeding
>100 if surgery at critical site e.g. the eye
contraindications for platelet transfusion?
bone marrow failure (chronic) ITP
heparin induced thrombocytopenia ITP
Inherited thrombophilias?
factor V Leiden (hetero/homo) - hetero most common (activated protein C resistance) Protein C deficiency Protein S deficiency Antithrombin III deficiency Prothrombin gene mutation
Acquired thrombophilias?
APLS
COCP
what is the most common bleeding disorder?
VWD
what is heparin induced thrombocytopenia?
AB form again PF4 and heparin after 5-10days of treatment with heparin
prothrombotic condition
S/S of HIT?
> 50% reduction in platelets
thrombosis
skin allergy
Mx HIT?
direct thrombin inhibitor
danaparoid
signs of transfusion reaction?
Fever low BP vomiting headache chestpain rigors dyspneoa urticaria collapse flushing pain at transfusion site itching
What are some causes of acute transfusion reactions? <24h
acute haemolytic reactions (ABO incompatibility) allergic/anaphylactic infection (bacterial) febrile non-haemolytic reaction respiratory (TACO, TRALI)
what are some causes of delayed transfuion reactions >24h?
delayed type haemolytic transfusion reactions infection (viral, malaria, vCJD) TA-GvHD (1-2w after transfusion) post transfusion purpura iron overload
Aetiology of febrile non-haemolytic transfusion reaction (FNHTR)?
release of cytokines from white cells during storage
S/S of FNHTR?
mild to mod reaction
small rise in temperature
chills, rigors
Mx FNHTR?
stop/slow transfusion
paracetamol
Aetiology allergic/anaphylactic transfusion reactions?
more common with FFP (proteins in plasma)
worst reaction if IgA deficient as anti-IgA abs in recipient attack the donor
S/S allergic/anaphylactic transfusion reactions?
mild itchy rash
anaphylaxis
Mx allergic/anaphylactic transfusion reactions?
stop/slow transfusion
mild (IV antihistamine)
anaphylaxis (adrenaline, ABC)
Aetiology ABO incompatibility/wrong blood?
IgM mediated intravascular haemolysis
S/S (acute haemolytic transfusion) ABO incompatibility/wrong blood?
septic looking restless chest/loin pain fever vomiting flushing haemoglobinuria
Ix ABO incompatibility/wrong blood?
FBC, XM, DAT
Mx ABO incompatibility/wrong blood?
stop transfusion
fluid resuscitation
Aetiology bacterial contamination transfusion reaction?
bacterial endotoxin build up in bag
platelets>RBC> FFP
S/S bacterial contamination transfusion reaction?
septic looking restless chest/loin pain fever vomiting flushing haemoglobinuria
S/S TACO?
Transfusion associated circulatory overload VERY COMMON SOB raised HR raised BP low O2 sats clinical fluid overload
Mx TACO?
Slow/stop transfusion
IV furosemide O2
TRALI presentation?
similar presentation to ARDS
FFP/plts>RBCs
mostly after infusion of plasma components
Aetiology TRALI?
anti-WBC AB in donor clump recipient WBCs
occurs within 6 hours of transfusion
S/S TRALI?
SOB Raised HR Raised BP low O2 fever normal CVP (0-6)
Ix TRALI?
CXR - bilateral pulmonary infiltrates
normal pulmonary arterial wedge pressure (PAWP)
Mx TRALI?
STOP transfusion
supportive
causes of prolonged PT?
Inherited: factor VII defieincy
acquired: vit K def, liver disease, warfarin, DIC
Causes of a prolonged APTT?
inherited: deficiency of VIII, IX, XI, XII, VWD
acquired: heparin, dabigatran, DOAC, acquired inhibitor of VIII, IX, XI or XII, acquired VWD, lupus anticoagulant
Causes of prolonged PT and APTT together?
inherited: prothrombin, fibrinogen, factor V/X deficiency
acquired: liver disease, DIC, severe vitamin K deficiency, anticoagulants ie combined warfarin and heparin, direct thrombin inhibitors
amyloidosis associated factor X deficiency
S/S G6PDD?
neonatal jaundice (<3/7 of life - most common requiring transfusion)
acute intravascular haemolytic precipitated by:
- infection
- drugs
- fava/broad beans
fever
abdo pain
malaise
dark urine
Ix G6PDD?
1st line ix = G6PDD levels now and in a month
nothing abnormal between acute episodes
raised G6PD during an acute episode - higher enzyme concentration in reticulocytes
reduced G6PD after the acute episode
blood film (acute) - heinz bodies, bite cells
Mx G6PDD?
Aware of signs of acute haemolysis (jaundice, pallor, dark urine)
avoidance of specific drugs, chemicals and foods
acute haemolysis: supportive care + folic acid
blood transfusion rarely required
Causes of neutropenia?
viral
- HIV
- Epstein-Barr virus
- hepatitis
drugs: cytotoxics,carbimazole, clozapine
benign ethnic neutropaenia:
common in people of black African and Afro-Caribbean ethnicity
requires no treatment
haematological malignancy: myelodysplastic malignancies
aplastic anemia
rheumatological conditions
systemic lupus erythematosus: mechanisms include circulating antineutrophil antibodies
rheumatoid arthritis: e.g. hypersplenism as in Felty’s syndrome
severe sepsis
haemodialysis
How does acute porphyria present?
abdominal pain, neurological symptoms such as motor neuropathy or paresis, and paranoid/delusional psychiatric disturbance
Diagnosis of porphyria?
classically urine turns deep red on standing
raised urinary porphobilinogen (elevated between attacks and to a greater extent during acute attacks)
assay of red cells for porphobilinogen deaminase
raised serum levels of delta aminolaevulinic acid and porphobilinogen
Mx porphyria?
avoiding triggers
acute attacks
- IV haematin/haem arginate
- IV glucose should be used if haematin/haem arginate is not immediately available
What are the complications of CLL?
anaemia
hypogammaglobulinaemia leading to recurrent infections
warm autoimmune haemolytic anaemia in 10-15% of patients
transformation to high-grade lymphoma (Richter’s transformation)
What is Ritcher’s transformation?
Ritcher’s transformation occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin’s lymphoma. Patients often become unwell very suddenly.
What symptoms are seen in Ritcher’s transformation?
lymph node swelling fever without infection weight loss night sweats nausea abdominal pain
What are some causes of DIC?
sepsis
trauma
obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome)
malignancy
What are tear drop poikilocytes associated with?
thalassaemia, megaloblastic anaemia and myelofibrosis
What is myelofibrosis?
a myeloproliferative disorder
thought to be caused by hyperplasia of abnormal megakaryocytes
the resultant release of platelet derived growth factor is thought to stimulate fibroblasts
haematopoiesis develops in the liver and spleen
features of myelofibrosis?
symptoms of anaemia e.g. fatigue (the most common presenting symptom)
massive splenomegaly
hypermetabolic symptoms: weight loss, night sweats etc
lab findings of myelofibrosis?
anaemia
high WBC and platelet count early in the disease
‘tear-drop’ poikilocytes on blood film
unobtainable bone marrow biopsy - ‘dry tap’ therefore trephine biopsy needed
high urate and LDH (reflect increased cell turnover)
what do you give for antiphospholipid syndrome in pregnancy
aspirin (low dose) and enoxaparin (discontinued at 34 w gestation)
What is ITP?
is an immune-mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.
S/S ITP?
Symptomatic patients may present with:
petichae, purpura
bleeding (e.g. epistaxis)
catastrophic bleeding (e.g. intracranial) is not a common presentation
Mx ITP?
first-line treatment for ITP is oral prednisolone
pooled normal human immunoglobulin (IVIG) may also be used
it raises the platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure is required
splenectomy is now less commonly used
What is Evans syndrome?
ITP in association with autoimmune haemolytic anaemia (AIHA)
Presentation CML?
anaemia: lethargy
weight loss and sweating are common
splenomegaly may be marked → abdo discomfort
an increase in granulocytes at different stages of maturation +/- thrombocytosis
decreased leukocyte alkaline phosphatase
may undergo blast transformation (AML in 80%, ALL in 20%)
management CML?
imatinib is now considered first-line treatment
inhibitor of the tyrosine kinase associated with the BCR-ABL defect
very high response rate in chronic phase CML
hydroxyurea
interferon-alpha
allogenic bone marrow transplant
what bleeding time results would you expect to see in VWD?
raised APTT
increased bleed time
normal INR and platelets
VWD inheritance?
autosomal dominant
Types of VWD?
type 1: partial reduction in vWF (80% of patients)
type 2*: abnormal form of vWF
type 3**: total lack of vWF (autosomal recessive)
Mx VWD?
tranexamic acid for mild bleeding
desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
factor VIII concentrate
what is polycythaemia vera associated with?
JAK2 mutation (95%)
what is polycythaemia vera?
Polycythaemia vera is a myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets
what are the typical features of polycytheamie?
hyperviscosity, pruritus and splenomegaly
what is the management of polycythaemia?
aspirin -reduces the risk of thrombotic events
venesection - first-line treatment to keep the haemoglobin in the normal range
chemotherapy
hydroxyurea - slight increased risk of secondary leukaemia
phosphorus-32 therapy
What is acute sickle chest syndrome?
dyspnoea, chest pain, pulmonary infiltrates, low pO2
the most common cause of death after childhood
what are the types of crisis associated with sickle cell?
thrombotic, 'painful crises' sequestration acute chest syndrome aplastic haemolytic
what is the management of lead poisoning?
dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
dimercaprol
features of lead poisoning?
abdominal pain peripheral neuropathy (mainly motor) fatigue constipation blue lines on gum margin (only 20% of adult patients, very rare in children)
Ix lead poisoning?
blood lead level (>10 = significant)
full blood count: microcytic anaemia.
Blood film: basophilic stippling and clover-leaf morphology
raised serum and urine levels of delta aminolaevulinic acid
urinary coproporphyrin is also increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased)
What is in cryoprecipitate?
factor VIII, fibrinogen, von Willebrand factor and factor XIII
Management of CLL?
Fludarabine and cyclophosphamide
Presentation of CML?
Often 60-70 years
anaemia: lethargy
weight loss and sweating are common
splenomegaly may be marked → abdo discomfort
an increase in granulocytes at different stages of maturation +/- thrombocytosis
decreased leukocyte alkaline phosphatase
may undergo blast transformation (AML in 80%, ALL in 20%)
Management of CML?
imatinib is now considered first-line treatment
inhibitor of the tyrosine kinase associated with the BCR-ABL defect
very high response rate in chronic phase CML
hydroxyurea
interferon-alpha
allogenic bone marrow transplant
prognosis of PRV?
thrombotic events are a significant cause of morbidity and mortality
5-15% of patients progress to myelofibrosis
5-15% of patients progress to acute leukaemia (risk increased with chemotherapy treatment)
What is the reversal agent for apixaban and rivaroxaban?
andexanet alfa
How is von willebrand inherited?
AD
Symptoms of VWD?
common: epistaxis and menorrhagia
rare: haemoarthroses and muscle haematomas
Types of VWD?
type 1: partial reduction in vWF (80% of patients)
type 2*: abnormal form of vWF
type 3**: total lack of vWF (autosomal recessive)
investigation of VWD?
prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristocetin
Management of VWD?
tranexamic acid for mild bleeding
desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
factor VIII concentrate
What are the symptoms of digoxin toxicity?
gastrointestinal disturbance (nausea, vomiting, abdominal pain), dizziness, confusion, blurry or yellow vision, and arrhythmias.
