Blood - Level 3 Flashcards
Pathology of DIC?
o Widespread activation of coagulation pathways
From release of procoagulants, formation of intravascular thrombi (fibrin)
Depletion of platelets and coagulation factors
• Then increased risk of bleeding
Causes of DIC?
o Malignancy – leukaemia o Sepsis o Trauma o Obstetric events – placental abruption, eclampsia, HELLP o Incompatible blood transfusion o Transplant rejection o Pancreatitis
Signs of DIC?
o Bruising
o Bleeding from at least 3 unrelated sites
o Renal failure – oliguria
o Hypotension
o ARDS
o In chronic/subacute – thrombotic events may dominate - VTE
Bloods in DIC?
o FBC – low platelets
o Clotting – raised PT and APTT, low fibrinogen
o Raised D-dimer
Blood films in DIC?
o Broken RBCs (fragments, paucity of platelets, schistocytes)
What is DIC scoring system?
o Measures platelets, D-dimer, PT, fibrinogen
5 or more – overt DIC – repeat daily
<5 – non-overt DIC – repeat net 1-2 days
Management of DIC - if low risk of bleeding?
o Treat cause
Management of DIC - if high risk of bleeding?
o Treat underlying cause
o Replace platelets
o FFP
2nd line - Cryoprecipitate to replace fibrinogen
o Activated Protein C – severe sepsis and multi-organ failure
Management of DIC - if dominant thrombotic signs?
o Unfractionated Heparin may be used – controversial
Complications of DIC?
o Haemorrhage
o Acute renal failure
o Gangrene and loss of digits
Definition of sickle cell disease?
- Inherited (autosomal recessive) blood disorder in which red blood cells develop abnormally
PAthology of sickle cell disease?
o Mutation in 17th nucleotide of Beta-globin gene changed from thymine to adenine and glutamic acid replaced by valine at position 6 in beta globin chain
o Abnormal beta-globin chain that causes it to polymerize when deoxygenated, which distorts the erythrocyte into a sickle shape
o Deformed erythrocytes form clusters which block blood vessels – damage large and small vessels, sequestered in liver and spleen and cause anaemia, intense pain and infections
What is sickle cell disease and sickle cell trait?
- Sickle cell disease
o Inherit HbS haemoglobin and gene for abnormal haemoglobin variant from other parent (homozygous HbSS, HbSC) - Sickle cell trait
o Inherit HbS haemoglobin and normal HbA haemoglobin (HbAS)
Epidemiology of sickle cell disease?
- Most common haemoglobinopathies
- 1 in every 2000 live births in England, and it is now the most common genetic condition at birth
- Highest prevalence of sickle cell disease is among Black African and Black Caribbean people
- Mortality rate 3% in childhood
Inheritance of sickle cell disease?
- Genetic, autosomal recessive – can be carrier or homogenous
Symptoms of sickle cell disease?
Moderate anaemia, pallor, lethargy, growth restriction with jaundice
Acute crises symptoms of sickle cell disease?
Increased susceptibility to encapsulated organisms (pneumococci, haemophilus influenzae, OSTEOMYELITIS due to Salmonella )
Acute painful Crisis
- Precipitated by cold, dehydration, excessive exercise/stress, hypoxia or infection
- Pain affecting many organs
- Dactylitis with swelling in hands/feet
- Commonest in limbs and spine
Acute chest syndrome
o Severe hypoxia, need ventilation and transfusion
Avascular necrosis
Acute anaemic crises
Priapism
Acute renal impairment
Acute stroke, hemiparesis, speech problems, seizures
Splenomegaly
Investigations in sickle cell disease?
Blood Tests o FBC, reticulocyte count - Blood film o Sickling of red cells
Hb electrophoresis (HPLC)= definitive test
Baseline tests
- U&E, LFT, lung function tests
When to admit acute crisis in sickle cell disease?
- Admission if clinical features of sickle cell crisis and raised temperature
Management of acute crisis in sickle cell disease?
Analgesia within 30 minutes of presentation and monitor
Bolus morphine if severe pain
• Weak opioid if moderate pain
Offer laxative, anti-emetic and antipruritic
Regular paracetamol and NSAIDs in addition
Monitor BP, HR, O2, RR, temperature regularly
Management of acute chest syndrome in sickle cell disease?
o Oxygen
o CPAP
o IV antibiotics
Management of priapism in acute crisis of sickle cell disease?
o Hydration
o Analgesia
o Aspiration and irrigation of corpora cavernosa with adrenaline if prolonged
Management at home if person well with mild pain and no increased temperature - what management measures?
o Avoid other triggers such as cold weather and excessive physical activity.
o Use distraction techniques, such as games, computers, and television
o Increase fluid intake (150% IV or oral)
o Prescribe paracetamol and/or ibuprofen (avoid ibuprofen if the person has renal impairment or significant proteinuria). Add codeine phosphate if these are not effective
o Urgent assessment in hospital if not controlled by these measures
When to screen for sickle cell disease?
- All newborn infant – Guthrie test
- Pregnant women -in high prevalence areas and low prevalence areas if high risk in Family Origins Questionnaire (FOQ)
- High-risk groups undergoing anaesthesia
- Women investigated for infertility
What vaccine to offer children with sickle cell disease?
Up to date with all immunisations
Pneumococcal vaccine at 2 and then every 5 years
Annual influenza vaccine
HepB vaccine at 12, 13 and 18 months
Men ACWY if travelling to high risk area
What vaccine to offer adults with sickle cell disease?
PPV every5 years
HepB on 0, 1 and 6 month schedule
Men ACWY if travelling to high risk area
When to offer antibiotics and folic acid in sickle cell disease?
- Antibiotics
o By 3 months of age:
Phenoxymethylpenicillin (erythromycin) - Oral folic acid to all 400mcg OD (5mg if pregnant/conceiving)
Chronic management of pain in sickle cell disease?
o Determine cause
o Refer to orthopaedic surgeon if persistent for MRI
o Regular medium/long-acting opiates and PRN for breakthrough
o NSAIDs
o CBT
Other chronic management in sickle cell disease?
- Smoking Cessation
- Yearly ophthalmology review and paediatric review
o If pulmonary hypertension – annual Echo - Managing minor priaprism:
o Empty bladder before sleep, jogging, warm baths, analgesia
o If >3 hours – hospital admission - Nocturnal Enuresis
o General advice
Ensure easy access to toilet, empty bladder just before sleep, reward system
o Oral/Nasal desmopressin for short-term
Advice to give people with sickle cell traits?
- Very rarely have symptoms
- Avoid high altitudes, such as travelling in an unpressurized aircraft
- Inform anaesthetist of sickle cell carriers
Secondary care management in sickle cell disease?
- Hydroxycarbamide in patients with severe disease
- Blood transfusion
Follow up in sickle cell disease?
Every 3 months for 1st 2 years then every 6 months til 5 then annually
Complications of sickle cell disease?
- Chronic pain
- Chronic anaemia
- Cognitive impairment
- Epilepsy
- Short stature and delayed puberty
- Adenotonsillar hypertrophy
- Cardiac enlargement and heart failure
- Renal dysfunction
- Pigment Gallstones
- In pregnancy:
o Miscarriage, premature labour, pre-eclampsia, stillbirth, IUGR, death
Prognosis of sickle cell disease?
- Depends on degree of sickle cell disease
o 90% of people survive past 20 - Stem cell transplant only potentially curative treatment
o Given if <17 with sickle brain disease which does nto response to hydroxycarbamide or severe sickle cell disease complications which does not respond to hydroxycarbamide
Description of haemophilia A & B?
- X-linked recessive blood disorder
- Haemophilia A = Factor VIII deficiency (most common)
- Haemophilia B = Factor IX deficiency
- Usually carrier females and affected males
Inheritance of haemophilia A & B?
- Most common inherited coagulation disorder
o Haemophilia A – 1 in 5000 live male births
o Haemophilia B - 1 in 30000 live male births - Males affected more common
Symptoms of haemophilia A & B?
- Most present towards end of first year of life
- Can present in neonatal period with intracranial haemorrhage, bleeding post-circumcision, oozing heel prick
Grading of haemophilia A & B?
o Severe: Spontaneous joint/muscle bleeds, arthropathy/arthritis, haematomas
o Moderate: Bleed after minor trauma
o Mild: Bleed after surgery
Investigations of haemophilia A & B?
- FBC
- Blood film
- Clotting tests
What clotting tests performed in haemophilia A & B?
Prothrombin Time (PT) Tests extrinsic system and expressed as INR, for abnormalities in Factors 1, 2, 5, 7, 10 Prolonged by warfarin, vitK deficiency, liver disease, DIC
Activated Partial Thromboplastin Time (APTT)
Tests intrinsic system, for abnormalities in Factor 1, 2, 5, 8, 9, 10, 11, 12
Prolonged by heparin, haemophilia, DIC and liver disease
Thrombin Time
Prolonged by heparin, DIC, dysfibrinogenaemia
D-Dimers
Fibrin degradation product, released during fibrinolysis
Occurs in DIC, DVT/PE but also malignancy and infection
Other tests to perform in haemophilia A&B?
- Factor 8 & 9 assays
o Diagnose by increased APTT and decreased FVIII/IX assay
Criteria for severity in haemophilia A&B?
o Mild – Factor levels of >0.05 but <0.40 IU/mL
o Moderate – Factor 0.01-0.05 IU/mL
o Severe – Factor <0.01 IU/mL
Management of Haemophilia A&B - prophylaxis, minor bleeds, major bleeds?
- Prophylaxis
o Infusions of Factor VIII/IX to prevent bleeding - Minor bleeds
o Pressure and elevation
o Desmopressin raises Factor VIII - Major bleeds
o Resuscitation
o Discuss need FFP and platelets with haematologist
o Recombinant Factor VIII/IX concentrate IVI
Home treatment can be taught
To 50% of normal (life-threatening bleeds need levels of 100%) - Avoid IM injections, NSAIDs and aspirin
- MDT approach , specialised physio to strengthen muscles and limit damage, psychosocial support and self-help groups
Complications of haemophilia?
- Inhibitors (antibodies to Factor VIII/IX)
o Reduce or inhibit effect of treatment - Transfusion transmitted infections
Physiology of haemoglobin?
- Most haemoglobin have two α chains and two other identical types
- HbA, the most common form of adult haemoglobin, has two α and two β chains
- Fetal haemoglobin (HbF) has two α and two γ components
Description of thalassaemia?
- Autosomal recessive condition characterised by decreased or absence of synthesis of one of the two polypeptide chains (α or β)
Types of thalassaemia?
o α-thalassaemia: reduced rate of α-chain synthesis.
Two alpha-genes on c16
o β-thalassaemia: reduced rate of β-chain synthesis
Due to lack of β-chain synthesis there is ↑ γ-chain synthesis beyond neonatal period ⇒ to more HbF and more HbA2 due to ↑ α-chain synthesis
Disease severity determined by levels of residual HbA and HbF
One B-globin gene on c11
Effects of thalassaemia?
- This precipitates in the RBC membrane bringing cell death within the bone marrow (ineffective erythropoiesis) and premature removal of red cells by spleen
Epidemiology of thalassaemia?
- β-thalassaemia
o Most common in Mediterranean and Middle east - A-thalassaemia
o South-east Asian origin
Types of B-thalassaemia?
o β-thalassaemia major
Most severe, HbA (α2β2) cannot be produced
o β-thalassaemia intermedia
Milder, mutation allows small amount of HbA and large amount of HbF to be produced
o β-thalassaemia trait
Heterozygotes usually asymptomatic, anaemia mild and red cells hypochromic and microcytic
Normal ferritin which distinguishes from iron deficiency anaemia
Types of A-thalassaemia?
o A-thalassaemia major (Barts hydrops fetalis)
Caused by deletion of all 4 A-globin chains so no HbA
Presents in mid-trimester with fetal hydrops (oedema and ascites) which is usually fatal
Need monthly transfusion intrauterine and after birth, usually fatal after birth
o A-thalassaemia HbH disease
Only 3 a-globin chains genes deleted
Mild-moderate anaemia but may need transfusions regularly
o A-thalassaemia trait
Deletion of 1 or 2 a-globin chains
Usually asymptomatic or mild anaemia – red cells microcytic, hypochromic
Symptoms of B-thalassaemia?
o Severe anaemia (hypochromic, microcytic cells) (transfusion dependent from 3-6 months), jaundice
o Failure to thrive
o Hepatosplenomegaly, bone marrow expansion, maxillary overgrowth
o Osteopenia, frontal bossing, skull x-ray shows ‘hair on end’ sign
Symptoms of A-thalassaemia?
o Major needs often transfusions and fatal in utero
o HbH
Moderate anaemia and features of haemolysis
Hepatosplenomegaly, leg ulcers, jaundice
o Alpha-thalassaemia trait
Mild anaemia and low RBC
Investigations in thalassaemia?
o FBC (microcytic, hypochromic anaemia), MCV (reduced) o Blood film o Iron (raised) o Hb electrophoresis - HbA2, HbF o Prenatal diagnosis offered
Imaging in thalassaemia?
o Skull XR – hair on end appearance, maxillary overgrowth, frontal bossing
o MRI used to monitor complications
Screening of thalassaemia?
o Pre-conceptual testing for haemoglobinopathies in at-risk groups
Family origin questionnaire
Management of thalassaemia?
o Promote fitness and healthy diet, folate supplements
o Regular blood transfusions to keep Hb >90
o Iron chelators (SC desferrioxamine/desferasirox)
o Splenectomy if hypersplenism persists and preferably >5 years old
o Bone marrow transplant only cure (reserved for HLA identical siblings)
Management during pregnancy in thalassaemia?
o Discontinue iron chelators 3 months before conception
o Folic Acid 5mg
o Serial biometry scans every 4 weeks from 24w-gestation
