Haematology Flashcards
What is anti-phospholipid syndrome?
An acquired disorder characterised by a predisposition to:
1. Both venous and arterial thromboses
2. Recurrent fetal loss
3. Thrombocytopenia
What is the aetiology of anti-phospholipid syndrome?
May occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE)
What diseases are associated with anti-phospholipid syndrome?
SLE
Other autoimmune disorders
Lymphoproliferative disorders
What are the features of anti-phospholipid syndrome?
- Venous/arterial thrombosis
- Recurrent fetal loss
- Lived reticularis (spasms of blood flow near the skin surface)
- Others: preeclampsia, pulmonary hypertension
What is the pathophysiology of anti-phospholipid syndrome?
Antibodies against anticardiolipin and anti-beta2 glycoprotein
What is the epidemiology of anti-phospholipid syndrome?
More common in young women
Accounts for 20% of strokes in < 45 years and 27% of women with more than 2 miscarriages
What are the investigations for anti-phospholipid syndrome?
- Autoantibodies: anticardiolipin, anti-beta2 glycoprotein I, lupus anticoagulant
- Thombocytopenia
- Paradoxical prolonged APTT
What is there a paradoxical rise in the APTT in anti-phospholipid syndrome?
Due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids in the coagulation cascade
What is the management for anti-phospholipid syndrome?
- Primary thromboprophylaxis = low dose aspirin
- Secondary thromboprophylaxis:
2a: initial VTE event = lifelong warfarin with a target INR of 2-3
2b: recurrent VTE events = lifelong warfarin consider adding low dose aspirin, increase INR target to 3-4
2c: Arterial thrombosis = lifelong warfarin with a target INR of 2-3
What is amyloidosis?
A (heterogenous) group of diseases characterised by extracellular deposition of insoluble amyloid fibrils
What are the two types of amyloidosis?
- AL amyloid = primary, immunoglobulin light chain amyloidosis, associated with Myeloma
- AA amyloid = secondary, non-familial and familial
2a. Non- familial AA = Inflammatory polyarthropathies account for 60% of cases, then chronic infections, IBD
2b. Familial AA = familial periodic Mediterranean fever syndrome
What are the risk factors for amyloidosis?
PMH of inflammatory conditions (AA)
Chronic infections (AA)
Positive FH
What are the features of primary amyloidosis (AL)?
Dependent on organ involvement:
1. Kidneys: glomerular lesions—proteinuria and nephrotic syndrome
2. Heart: restrictive cardiomyopathy (looks ‘sparkling’ on echo), arrhythmias, angina
3. Nerves: peripheral and autonomic neuropathy; carpal tunnel syndrome
4. GI: macroglossia (big tongue), malabsorption/weight, perforation, haemorrhage, obstruction, and hepatomegaly
5. Vascular: purpura, especially periorbital—a characteristic feature
What are the features of secondary non-familial amyloidosis (AA)?
PMH of chronic inflammation (e.g. RA/ IBD) or chronic infection (e.g. TB)
Affects the kidneys, liver, and spleen, and may present with proteinuria, nephrotic syndrome, or hepatosplenomegaly
Macroglossia is not seen; cardiac involvement is rare
What are the appropriate investigations for amyloidosis?
Diagnosis made with biopsy of affected tissue: positive Congo Red staining with apple-green birefringence under polarized light microscopy
The rectum or subcutaneous fat are relatively non-invasive sites for biopsy and are positive in 80%
Can also use serum amyloid precursor (SAP) scan
What is the management of amyloidosis?
AL: optimize nutrition; PO melphalan + prednisolone extends survival
High-dose IV melphalan with autologous stem cell transplantation may be better
AA: manage the underlying condition optimally
What is the prognosis of patients with amyloidosis?
Median survival is 1–2 years
Patients with myeloma and amyloidosis have a shorter survival than those with myeloma alone
What is aplastic anaemia?
Characterised by pancytopenia and a hypoplastic bone marrow (deficiency of all blood cell elements, no abnormal cells)
What is the peak incidence of acquired aplastic anaemia?
30 years old
What are the causes of aplastic anaemia?
- Idiopathic (>40%)
- Congenital: falcon anaemia
- Drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin
- Toxins: benzene
- Infections: parvovirus, hepatitis
- Radiation
What is the onset of features for aplastic anaemia?
Can be slow (months) or rapid (number of days)
What are the features of aplastic anaemia?
Normochromic, normocytic anaemia:
1. Tiredness
2. Lethargy
3. Dyspnoea
Thrombocytopaenia:
1. Easy bruising
2. Bleeding gums
3. Epistaxis
Leukopenia:
Increased frequency and severity of infections
What are the investigations for aplastic anaemia?
Bloods- FBC: 2 or more cytopenias among the following:
1. Hb < 100
2. Platelets < 50
3. Absolute neutrophil count <1.5
Reticulocyte count: low or absent
Bone marrow biopsy:
1. Hypocellular marrow with no abnormal cell population
2. Marrow space is composed mostly of fat cells and marrow stroma
Exclude other causes e.g. lymphoma, leukaemia : do a blood film
What is the criteria for severe aplastic anaemia?
Marrow showing <25 % of normal cellularity
OR
Marrow showing <50 % of normal cellularity, <30% of the cells are haematopoietic plus 2 of the following:
1. neutrophils < 0.5x10⁹/L
2. platelets < 20x10⁹/L
3. reticulocytes < 40x10⁹/L
What is the management for aplastic anaemia?
Treat the underlying cause
If no cause, management options include:
1. Blood transfusions
2. Stem cell (bone marrow ) transplant
3. Immunosuppressants
Others: antibiotics
What is a blood product transfusion?
A lifesaving procedure to treat hemorrhages and to improve oxygen delivery to tissues
What different blood products can be transfused?
- Packed red cells: for chronic anaemia
- Platelet rich plasma: for patients who are thrombocytopaenic and are bleeding or require surgery
- Platelet concentrate: for thrombocytopaenia
- Fresh frozen plasma: used in correcting clotting deficiencies in patients with hepatic synthetic failure who are due to undergo surgery
- Cryoprecipitate: Rich source of Factor VIII and fibrinogen
Which blood products must be cross matched?
- Packed red cells
- Fresh frozen plasma
- Cryoprecipitate
- Whole blood
(platelets can be ABO incompatible in adults)
What blood products are used in warfarin reversal?
- Stop warfarin
- Vitamin K (reversal within 4-24 hours, IV is quicker than oral)
- Fresh frozen plasma
- Human prothrombin complex (now first line for warfarin reversal, reversal within 1 hour)
What are the indications for red cell transfusions?
- Symptomatic anemia (causing shortness of breath, dizziness, congestive heart failure, and decreased exercise tolerance)
- Acute sickle cell crisis
- Acute blood loss of more than 30 percent of blood volume
What are the indications for fresh frozen plasma transfusion?
Can be used for reversal of anticoagulant effects e.g. warfarin (but less commonly used)
What are the indications for platelet transfusion?
To prevent haemorrhage in patients with thrombocytopenia or platelet function defects
What are the indications for cryoprecipitate transfusion?
Used in cases of hypofibrinogenemia, which most often occurs in the setting of massive hemorrhage or consumptive coagulopathy
How can the complications of blood product transfusions be classified?
- Immunological: acute haemolytic, non-haemolytic febrile, allergic/ anaphylaxis
- Infective
- Transfusion related acute lung injury (TRALI)
- Transfusion associated circulatory overload (TACO)
Others: hyperkalaemia, iron overload, clotting
What is non-haemolytic febrile reaction following a blood transfusion?
Thought to be caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage
Features:
1. Fever
2. Chills
Management:
1. Stop or slow the transfusion
2. Paracetamol
3. Monitor
What is a minor allergic reaction following a blood transfusion?
Thought to be caused by foreign plasma proteins
Features:
1. Pruritus
2. Utricaria
Management:
1. Temporarily stop the transfusion
2. Anti-histamine
3. Monitor
What is an anaphylactic reaction following a blood transfusion?
Can be caused by patients with an IgA deficiency who have anti-IgA antibodies
Features:
1. Hypotension
2. Dyspnoea
3. Wheezing
4. Angioedema
Management:
1. Stop the transfusion
2. A to E approach (oxygen, fluids)
3. IM adrenaline
What is an acute haemolytic reaction following a blood transfusion?
ABO incompatible blood e.g. secondary to human error
Features:
1. Fever
2. Abdominal pain
3. Hypotension
Management:
1. Stop the transfusion
2. Confirm diagnosis: check blood product against patient name, send blood for Coombs test
3. Supportive care: fluid resuscitation
What is TACO following a blood transfusion?
Transfusion-associated circulatory overload from an excessive rate of transfusion/ pre-existing HF
Features:
1. Pulmonary oedema
2. Hypertension
Management:
1. Slow or stop transfusion
2. Consider IV loop diuretic e.g. furosemide and oxygen
What is TRALI following a blood transfusion?
Transfusion related acute lung injury: non-cardiogenic pulmonary oedema from increased vascular permeability
Features:
1. Hypoxia
2. Pulmonary infiltrates on chest x-ray
3. Fever
4. Hypotension
Management:
1. Stop the transfusion
2. Supportive care and oxygen
What transfusion reactions require stopping the transfusion ?
- Minor allergic reaction (temporarily)
- Anaphylaxis
- Acute haemolytic reaction
- TRALI
What is the key difference between TACO and TRALI following a blood transfusion?
TACO: hypertensive, TRALI: hypotensive
Both have pulmonary oedema but one is from circulatory overload (TACO) and one is non-cardiogenic (TRALI)
What is the Hb threshold to require a red blood cell transfusion?
Without ACS:
70 g/L (target for 70-90)
With ACS:
80 g/L (target for 80-100)
What is a bone marrow aspirate?
A procedure in which a small sample of bone marrow is removed, usually from the hip bone, breastbone, or thigh bone e.g. Luekaemia, multiple myeloma, polycythaemia, bone marrow failure
What is haemolytic uraemic syndrome?
Generally seen in young children and produces a triad of:
1. Acute kidney injury
2. Microangiopathic haemolytic anaemia
3. Thrombocytopenia
What are the two types of haemolytic uraemic syndrome?
- Primary: (less common), also known as ‘atypical’) is due to complement dysregulation
- Secondary: (most cases, typical HUS)
a. Classically Shiga toxin-producing Escherichia coli (STEC) 0157:H7
b. Pneumococcal infection
c. HIV
d. Rare: SLE, drugs, cancer