revision seminar - haematology general haematology ... lecture (inc...revision seminar - haematology...
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Revision Seminar - Haematology General Haematology Haemostasis & Thrombosis Remember: The most important investigation is the clinical
history and any relevant family history A normal blood test does not exclude significant
pathology
Blood Tests FBC
Collect into EDTA
Coagulation investigations Collect into citrate 1+9 ratio of anticoagulant:blood is crucial
Don’t forget the age/ethnic origin of the patient
Differential diagnosis may be different Reference ranges are different
Anaemia – what you need to know Anaemia: Classification/investigation/management
Microcytic anaemias Macrocytic anaemias Normocytic anaemias
Key disorders – Presentation/Diagnosis/Management
Iron deficiency anaemia B12/Folate deficiency Haemolytic anaemias esp. AIHA Anaemia of chronic disease Thalassaemias [Alpha and Beta] Sickle Cell Disease
Anaemia Hb
Are the WCC/Differential WCC and Platelet count normal ? Anaemia or Pancytopaenia
Differential diagnosis is different
MCV ↓ - Microcytic
Fe-deficiency Anaemia Thalassaemia
↑ - Macrocytic B12/Folate deficiency Know what these do and how/where Drugs they are absorbed Liver disease Haemolysis
N - Normocytic Anaemia of chronic disease [Occ. microcytic] MDS
Case 1
Comment upon the results of these investigations? What is the differential diagnosis of a hypochromic, microcytic anaemia? How would you investigate such a patient?
Parameter Patient Reference Range WBC 6.1 x 109/L 5 -10 x 109/L Differential WCC Normal Hb 82 g/L 130 - 170 g/L MCV 69 fl 80 -100 fL Platelets 490 x 109/L 150 - 400 x 109/L Film Hypochromic Microcytic Red Cells
Male Age: 65 years Source: Surgical Outpatients History: Intermittent diarrhoea
Morphology: Iron Deficiency
Hypochromic Microcytic
Iron
Absorption Storage Tests MCV Serum Ferritin Serum Fe TIBC % Saturation
Iron and Measurements MCV Serum Ferritin Serum Fe Transferrin & TIBC % Percentage Saturation
Iron Serum Iron
Iron circulates in plasma bound to the transport protein Transferrin. Transferrin binds two atoms of Fe3+ and delivers iron to cells by
interacting with a surface membrane transferrin receptor. Considerable variation in the levels throughout the day and from
individual-to-individual
↓ Serum Iron ↑ Serum Iron Iron deficiency anaemia Iron overload Anaemia of chronic disease Liver disease
Acute phase protein
Iron Total Iron Binding Capacity [TIBC] In plasma, iron is bound to Transferrin and the measurement of Total Iron Binding Capacity [TIBC] is a measure of transferrin concentration Transferrin Can be measured immunologically Transferrin Saturation A Transferrin saturation of 30% implies that 30% of the binding sites on Transferrin are occupied with iron.
↓ Transferrin Saturation ↑ Transferrin Saturation
Iron deficiency anaemia Haemochromatosis
Iron Ferritin Storage form of iron Measurement of serum ferritin is a marker of iron stores ↓ Ferritin: Consistent with depletion of iron stores ↑ Ferritin: Iron overload - Repeated transfusion - Haemochromatosis Ferritin is an acute phase protein and its level may be misleadingly high in the context of an acute phase response
What else to think about if you encounter a patient with microcytic blood picture
Thalassaemia HbA: α2β2
HbA2: α2δ2
HbF: α2γ2
Beta-Thalassaemia
Alpha-Thalassaemia
Alpha-Thalassaemia
Alpha-Thalassaemia
β-Thalassaemia Minor or Trait Heterozygous mutation ↓MCV ↑ HbA2 Major Homozygous or compound heterozygous mutations Excess α-chains Present within the first 2 years of life Severe hypochromic microcytic anaemia Multiple problems if not transfused Commonly transfusion dependent [-> iron overload]
HbA α2β2 HbF α2γ2
HbA2 α2δ2
α-Thalassaemia Single gene deletion Silent carriers MCV may be reduced
Two gene deletion Mild microcytic anaemia
Three gene deletion Excess β-chains -> Hb H [β4 tetramers]
-> Hb Barts [γ4 tetramers]
Four gene deletion Excess β-chains -> Hydrops fetalis
HbA α2β2 HbF α2γ2
HbA2 α2δ2
Hbaemoglobinopathies [Sickle Cell Disease]
Amino acid substitutions that lead to e.g. Hb AS or HbSS [there are numerous Hb’opathies]
Deoxygenation of HbSS leads to crystal formation [tactoids] – distort red cell membrane
Problems [Hypoxia/acidosis/hypothermia/infection/dehydration] -> Painful crises/chest crises/stroke Priapism Aplastic crises [B19] Infections [asplenic/salmonella]
Case 2
1. Comment upon the results of these investigations? 2. What are the causes of a pancytopenia? 3. What are the causes of a macrocytosis?
Parameter Patient Reference Range WBC 3.1 x 109/L 5 -10 x 109/L Differential WCC Normal Hb 61g/L 130 - 170 g/L MCV 121 fl 80 -100 fL Platelets 97 x 109/L 150 - 400 x 109/L Film Macrocytes and hypersegmented neutrophils
Female Age: 55 years Source: GP History: ??Jaundiced
Pancytopaenia
Drugs or Toxins Environmental exposure Severe B12 and/or folate deficiency Viruses Hypersplenism Idiopathic [Immune] – Aplastic Anaemia Leukaemia/Marrow infiltration Congenital Others…
Work-up….
Morphology: Macrocytosis
B12/folate deficiency Liver disease Alcohol Drugs Other…
B12 Deficiency Megaloblastic Bone Marrow
B12/Folate
Case 2
Parameter Patient Reference Range WBC 3.1 x 109/L 5 -10 x 109/L Differential WCC Normal Hb 61 g/L 130 - 170 g/L MCV 121 fl 80 -100 fL Platelets 97 x 109/L 150 - 400 x 109/L Film Macrocytes and hypersegmented neutrophils
Female Age: 55 years Source: GP History: ??Jaundiced
1. The Vitamin B12 level on this patient is 92ng/L [NR: 211-911 ng/L]
2. Discuss the investigation and management of a patient with a megaloblastic anaemia?
3. Why is this patient jaundiced?
Case 3
1. Describe these results 2. How would you investigate this patient and what additional tests would you
request? 3. Describe the causes of haemolysis. 5. Outline the principles of the Direct and Indirect Antiglobulin (‘Coombs’) test 4. How would you manage a patient with haemolysis?
Parameter Patient Reference Range WBC 9.2 x 109/L 5 -10 x 109/L Differential WCC Normal Hb 72 g/L 130 - 170 g/L MCV 105 fl 80 -100 fL Platelets 400 x 109/L 150 - 400 x 109/L Reticulocytes 350 x 109/L 80-120 x 109/L Film Spherocytes ++ Marked polychromasia
Female Age: 45 years Source: GP History: ??Jaundiced
Morphology: Polychromasia & Spherocytes
Reticulocyte
Spherocyte
Morphology: Anisocytosis & Poikilocytosis
Mechanical heart valve
Direct and Indirect Antiglobulin [‘Coombs’] Test
Direct [DAGT]
Indirect [IAGT]
Case 4
1. Comment upon the blood indices 2. What other tests would you request? 3. If the tests demonstrated impaired renal function how would you manage the
anaemia?
Parameter Patient Reference Range WBC 11.2 x 109/L 5 -10 x 109/L Differential WCC Normal Hb 92 g/L 130 - 170 g/L MCV 87fl 80 -100 fL Platelets 281 x 109/L 150 - 400 x 109/L Reticulocytes 40 x 109/L 80-120 x 109/L Film Normochromic Normocytic red cells
Female Age: 67-years-old Source: GP History: Tired
Normochromic/Normocytic Anaemia
Thrombocytopaenia Artefact Check film + Citrate count MPV Increased peripheral destruction Production problem Check other parameters ?Pancytopaenia History Drugs/Family History/Bleeding History Causes Artefact Production Problem Destruction Problem Drugs Drugs Viral Viral Idiopathic/Immune Idiopathic/Immune Bone marrow failure Hypersplenism Congenital [Rare] Others DIC/TTP/Dilutional B12/Folate deficiency
Neutropaenia Ethnic origin of the patient Isolated neutropaenia or other FBC abnormalities Causes Drugs/toxins/chemicals Idiopathic Bone marrow problem – primary/secondary Viral infection B12/Folate deficiency Hypersplenism Congenital - rare
Extra - 1 A 4-year-old boy is seen in the ED with a painful right leg.
His blood film shows:
1. What is the diagnosis?
2. What infections are these individuals prone to?
Extra - 2 A 20-year-old medical student spends his elective in Africa. He presents to casualty on his return with general malaise and a pyrexia. A blood film shows the following:
1. What is the diagnosis? 2. What should he/she have done?
Haemostasis, Thrombosis and Anticoagulants
Overview of Haemostasis Inherited & Acquired Bleeding Disorders Thrombosis and Risk Factors Anticoagulants
What do you need to know?
Haemostasis Primary haemostasis [Role of platelets and Von Willebrand Factor] Clotting cascade [Generation of a fibrin clot] Fibrinolysis [Breakdown of the fibrin clot]
Tests of Haemostasis Bleeding History Platelet Count PT/APTT/Fibrinogen D Dimers
What do you need to know? Inherited Bleeding Disorders
Haemophilia A & B Von Willebrand Disease [What are they/Classification/Presentation/Principles of treatment]
Acquired Bleeding Disorders Drugs [anticoagulants] Liver disease Massive blood transfusion Vitamin K deficiency [incl. haemorrhagic disease of the newborn] Disseminated Intravascular Coagulation [DIC]
What do you need to know? Thrombosis
Risk factors [Inherited and acquired] Common presentations [DVT/PE] Diagnosis [including role of D Dimer] Management Thromboprophylaxis
Anticoagulants: Indications/monitoring/complications Heparins [UFH/LMWH/Fondaparinux] Warfarin Newer anticoagulants [Dabigatran/Rivaroxaban] Antiplatelet agents [Aspirin & Clopidogrel]
Normal Haemostasis
Constriction of blood vessels reduces blood flow
Platelets, VWF & the Vascular Endothelium
Platelets
Resting
Activated
Spread
Coagulation Cascade
PL – Platelet Membrane Phospholipid TF - Tissue Factor ‘a’ – active enzyme
Biological amplification system Incredibly efficient: 1 mole XIa generates ~107 moles IIa Clotting factors numbered I - XIII Factors II, VII, IX & X require a post-translational
modification [gamma carboxylation] Most clotting factors (except V, VIII and XIII) are
serine proteases Phospholipid derived from activated platelet
membrane
The Coagulation Cascade Binding of FVII to Tissue Factor (TF) initiates coagulation → Generates trace amounts of thrombin (IIa) → Activates FIX to XIa FV to Va FVIII to VIIIa → Massive but highly focused burst of thrombin → Rapidly converts soluble
fibrinogen to insoluble fibrin → Fibrin reinforces and
stabilises the platelet ‘plug’
PT APTT
Tests: PT and APTT Principles….
Citrated blood Centrifuged -> Platelet poor plasma + Activator + Platelet substitute + Calcium ->Measure time to clot formation
Any investigation of haemostasis MUST include a platelet count
Case 2 An 18-month old boy is referred by his GP with a
short history of a painful, swollen left knee. Investigations:
Full Blood Count Normal Prothrombin Time [PT] 13s [12-15s] Activated Partial Thromboplastin Time (APTT)
93s [27-35s]
Case 2 An 18-month old boy is referred by his GP with a
short history of a painful, swollen left knee. Investigations:
Full Blood Count Normal Prothrombin Time [PT] 13s [12-15s] Activated Partial Thromboplastin Time (APTT)
93s [27-35s]
Factor VIII <1 IU/dl [45-150 IU/dl]
PT APTT
Tests: PT and APTT
Diagnosis: Severe Haemophilia A
Haemophilia A & B X-linked disorders Males affected Females – carriers and usually asymptomatic
Classified by Factor Levels Severe < 1 IU/dL Recurrent joint/muscle
bleeds Moderate 1-5 IU/dL Bleed after trauma Mild > 5 IU/dL Bleed after trauma Treatment Haemophilia A Severe rFVIII Mild/Moderate rFVIII or DDAVP Haemophilia B rFIX
Von Willebrands Disease [vWD]
Von Willebrand Factor [VWF] Carrier protein for FVIII Involved in platelet-endothelial cell interaction
Classification Type 1 80% Cases: Quantitative deficiency functionally normal VWF Type 2 10-15% cases: Qualitative deficiency Type 3 Rare – no VWF Bleeding problems Mucocutaneous bleeding Treatment Plasma-derived VWF-containing concentrate DDAVP Tranexamic Acid
Why do Patients Bleed? Inherited Bleeding Disorders - Rare Acquired Bleeding Disorders - Common Drugs Liver disease Vitamin K deficiency Disseminated intravascular coagulation Dilutional coagulopathy Surgical trauma Miscellaneous e.g. C-P Bypass, renal disease
Who do Patients Bleed?
Drugs
Case 4 A 7-day old baby born at home is found
unconscious and bleeding from his nose and mouth. Clotting tests show:
PT 98s [↑↑] APTT 102s [↑↑]
Fibrinogen 2.9 g/L [N] Platelets 288 x 109/L [N] Why do you think might be the problem and why?
PT APTT
Tests: PT and APTT
Diagnosis: Vitamin K Deficiency – Haemorrhagic Disease of the Newborn
Case 4 Vitamin K omitted at delivery
No transplacental passage of Vitamin K Immature liver Sterile gut Very little Vitamin K in breast milk
All babies should receive I.M. Vitamin K at birth
Massive Transfusion Definition: Loss of 1 blood volume in <24hrs Blood loss >150ml/min >50% blood loss within 3hr Problems arise due to: Red cells no clotting factors No platelets Cold blood Acidosis Citrate toxicity
Disseminated Intravascular Coagulation (DIC) Inappropriate and continuing activation of
coagulation Activation leads to:
→ Microvascular thrombi formation & tissue damage → Consumption of coagulation factors and bleeding
Disseminated Intravascular Coagulation Mechanisms
- Procoagulant material released into the circulation Amniotic fluid embolus, ABO incompatibility mucin secreting CA, AML, extensive trauma, burns - Severe endothelial damage and tissue factor expression
Gram -ve sepsis, viral infections, burns - Direct platelet activation
Bacterial and viral immune complexes - Direct activation of coagulation
Snake bite
Disseminated Intravascular Coagulation 1o consequences of activation
Thrombin generation Fibrinogen to fibrin Excess thrombin exceeds inhibitory mechanisms
Platelet activation Platelet aggregation Formation of:
Microvascular thrombi → end organ damage Loose fibrin sieve/mesh → haemolysis
Disseminated Intravascular Coagulation
2o consequences of activation Activation of fibrinolysis
Breakdown of fibrinogen ↑FDPs (D-dimer) Continued consumption & activation
[Consumption exceeds production]
Depletion of coagulation factors, fibrinogen, platelets Bleeding from wounds, venepuncture sites, bruising ++
Disseminated Intravascular Coagulation
Laboratory features ↑PT & ↑APTT ↑TT ↓Platelet count ↓Fibrinogen ↑Raised FDP and D-dimer Evidence of microvascular haemolysis
Disseminated Intravascular Coagulation Management
1. Treat the underlying disorder 2. Treat the coagulopathy Blood product replacement
FFP, cryoprecipitate, platelets
Massive Transfusion/DIC
PT APTT Fibrinogen Haemoglobin
Platelet count
It’s the history that is important
Venous Thromboembolic Disease
USA: 1:1,000 pa clinically significant DVTs 250,000 hospitalisations annually due to VTED
Risk of recurrence: 5 years 35-30%
Fatal PE: UK: 20-30% medical patients at PM have PE as a cause/contributory cause of death
PE: Commonest cause of death in pregnancy
Requirement that all patients admitted to hospital have a VTE risk assessment performed
Why do thromboses develop?
Pathophysiology of thrombosis involves:
Changes in the vessel wall
Atheromatous plagues
Anti-platelet drugs
Changes in blood flow
Atrial fibrillation Warfarin/Aspirin
Changes in the blood constituents
Miscellaneous Nil, Aspirin, Warfarin
Virchow’s Triad
Risk Factors for DVT/PE [VTE] Obesity Immobility including surgery/trauma OCP/HRT Pregnancy Cancer Previous thrombosis Family history VTE Age Male sex
Inherited risk factors
VTED: Diagnosis Clinical History Signs & Symptoms Clinical Probability Score Confirmatory tests
DVT PE D Dimer D Dimer U/S CT-PA Ventilation-Perfusion (V/Q) Scan ECG [R heart strain] CXR Blood gases
Fibrinolysis Fibrinolysis - the
breakdown of blood clots
D-Dimers
Why measure D-dimer?
High negative predictive value Low positive predictive value
- Can exclude a DVT/PE but not
diagnose it
Combine with clinical pre-test clinical probability score to exclude DVT
Wells Score for DVT [NICE]
Wells Score for PE [NICE]
How do we treat a DVT/PE? Currently available anticoagulants Parenteral anticoagulants
[Unfractionated heparin (UFH)]
Low Molecular Weight Heparin (LMWH) Fondaparinux
Oral anticoagulants [Vitamin K antagonists] Warfarin
Direct Oral Anticoagulants Dabigatran – Direct Thrombin [IIa] Inhibitor Rivaroxaban/Apixaban – Direct Factor Xa inhibitors
Heparin Unfractionated heparin [UFH] Inhibits thrombin and factor Xa
Usually given by iv infusion Monitor by means of APTT In-patient treatment only Rapidly reversed
Low Molecular Weight Heparin [LMWH] Inhibits factor Xa SC administration Monitor using Anti-Xa assay (if necessary) Predictable pharmacokinetics Fewer side-effects Widely used for out-patient treatment
Side-effects of Heparin Bleeding [Less rare]
2-3% of patients receiving heparin Risk increased if additional risk factors for bleeding
Osteoporosis [Rare] Heparin-induced thrombocytopaenia [Rare]
Warfarin Most widely prescribed oral anticoagulant 1:75 of the UK population on warfarin
Bleeding Risk 1:100 per annum 1:400 fatal bleeding risk per annum
Frequent monitoring required INR
Teratogenic
Warfarin: Mechanism of Action
Vitamin K
Warfarin
Synthesis of Dysfunctional Coagulation
Factors
VII IX X II
Vitamin K Utilization Reduced
Monitoring Warfarin
INR: International Normalised Ratio
ISI: International Sensitivity Index
All reagents corrected for sensitivity of the test reagents
Therapeutic Ranges Target INR 2.5 [range 2-3] DVT/PE/AF/Valvular heart disease
Target INR 3.5 [range 3-4.5] Some Prosthetic heart valves
Direct Oral Anticoagulants
Licensed Indications 1. Non-valvular Atrial Fibrillation
2. Treatment VTED 3. Surgical thromboprophylaxis
Direct Oral Anticoagulants
Case 6 A 24-year-old male is admitted to casualty with
widespread bruising and bleeding from his gut. Investigations: Hb 72 g/L Platelets 190 x 109/L PT >120s APTT >120s
What questions might you ask? How would you manage this problem?
PT APTT
Tests: PT and APTT Diagnosis: Rodenticide poisoning Treatment: Vitamin K Clotting factor replacement
A 34-year-old woman presents with a 4-week history of increasing lethargy, breathlessness and more recently has noticed herself to be bruising easily.
Full Blood Count Hb 73 g/L WCC 1.2 x 109/L Platelets 25 x 109/L
Haematology
Comment upon these investigations and suggest possible diagnoses
Haematology
Comment upon this bone marrow aspirate.
Suggest a diagnosis.
Give 4 possible causes for this disorder.
How would you manage this?
Haematology
Thanks to your care, your patient makes a complete recovery and is discharged from further follow-up.
However, 4 years later she presents to her GP with increasing breathlessness and fatigue.
Full Blood Count Hb 69 g/L MCV 56fl WCC 9.4 x 109/L Platelets 259 x 109/L
What questions might you ask?
What else might you request?
Haematology
What abnormality(ies) are shown in this blood film?
What would be important to ask in the history?
What tests might you request to confirm the diagnosis?
You request a blood film (amongst other things)
Haematology
Your investigations show: Ferritin 2µg/L PT 13s APTT 49s VIII:C 23u/dl vWF:Ag 20u/dl vWF:Act 21u/dl
1. What do these tests suggest? 2. Are there any additional tests
you might request? 3. What is the diagnosis? 4. How would you manage this
lady?
Haematology
Once again (!) thanks to your outstanding care your patient makes a complete recovery and is discharged from further follow-up.
However, many years later now aged 68, she presents to her GP with increasing breathlessness and fatigue. On examination she is pale and appears slightly jaundiced.
Full Blood Count Hb 56 g/L MCV 118fl WCC 1.2 x 109/L Platelets 91 x 109/L
What do these tests suggest and what else might you request?
Haematology
1. What does this blood film show?
2. What further tests
would you request? 3. What is the most likely
diagnosis and how would you treat this lady?
You request a blood film (amongst other things)
Haematology Serum B12 98ng/l GPC antibodies Positive IF antibodies >100U/ml
Haematology
Once again (!) thanks to your outstanding care your patient makes a complete recovery and is discharged to the care of her GP.
However, she presents with symptoms reminiscent of her first problem - increasing lethargy & breathlessness
Full Blood Count Hb 67 g/L MCV 103fl WCC 9.4 x 109/L Platelets 234 x 109/L Retics 467 x 109/L
What do these tests suggest and what might you request?
Haematology
Additional Investigations LDH 3467 U/L Bilirubin 123 umol/L Blood Film ………………….. Direct Antiglobulin Test [‘Coombs’] IgG 4+
Haematology Diagnosis: Autoimmune haemolytic anaemia Q: Outline the principles of the Direct and Indirect
AGT How would you manage this lady?
Direct and Indirect AGT
Haematology
Once again (!) thanks to your outstanding care your patient makes a complete recovery and she is discharged to the care of her GP.
However, she presents with symptoms reminiscent of her first problem - increasing lethargy, breathlessness and easy bruising.
Full Blood Count Hb 83 g/L MCV 94fl WCC 78.2 x 109/L Platelets 34 x 109/L
What do these tests suggest and what might you request?
Haematology
1. What does this blood film show?
2. What is the diagnosis?
You request a blood film (amongst other things)
Haematology
What is the blood group?
Blood group serology Typing antisera + patients cells
Anti-A Anti-B Anti-A+B Anti-D ++ - ++ ++
Typing cells + patients sera
A cells B cells - ++
‘++’ = agglutination ‘-’ = no agglutination
Haematology In spite of your best care, your patient dies. A PM is requested. What does this show? What risk factors does this lady
have that might predispose her to this condition?
Symptoms Suggesting a Coagulation Disorder
Recurrent bleeding following trauma/surgery
Menorrhagia/post-partum bleeding Repeated epistaxes Unexplained purpura Simultaneous bleeding from several sites
Recurrent, chronic bruising
Neonatal Haemostasis Neonates have ‘abnormal’ coagulation
– Low levels of coagulation factors – Low levels of vitamin K dependent factors – Abnormal fibrinogen
Prolonged APTT, PT, TT Different reference ranges for neonates (until 6/12)
Part 2 ………..
Case 1 A 10-day-old boy born at home is found unconscious by his
parents. He is noted to be bleeding from his nose. Investigations show: Prothrombin Time: >120s APTT: >120s Fibrinogen: 3.4g/L What is the most likely diagnosis? How would you treat this? How does this disorder arise?
1. Multiple clotting factor deficiencies or common pathway
Most likely Vitamin K deficiency
2. FFP/vitamin K
3. No transplacental passage VK
Sterile gut
No VK in breast milk
Hepatic immaturity
Case 2
A 23-year-old woman is admitted via A & E having been found collapsed in the street. She has a widespread non-blanching rash.
A coagulation screen shows: PT: 34s APTT: 78s Fibrinogen: 0.5g/L Thrombin time: 61s D-dimers: 2000µg/L Platelets: 34 x 109/L
Diagnostic of DIC
Case 2 contd.
What do you think the diagnosis is? How would you manage this problem? What other causes of this coagulation problem are
you aware of? How does this disorder arise?
1. DIC secondary to meningococcal sepsis
2. Treat underlying cause
Active resuscitation + FFP/Platelets/Fibrinogen
3. Multiple
- Exposure of TF
- Release of Tissue factor into the circulation
- Endotoxins
Case 3 An 18-year-old woman seeks your advice because of a
history of fatigue, menorrhagia and easy bruising Investigations show: Hb 7.4g/dl MCV 58fl PT 13s APTT 48s VIII:C 0.25 IU/ml [NR: 0.45-1.49] VWF:Ag 0.21 IU/ml [NR: 0.48-1.55] VWF:Act 0.20 IU/ml [NR: 0.5-1.50]
1. Microcytic anaemia
2. Prolonged APTT - therefore must be def of VIII, IX, XI (or XII) or a Lupus Anticoagulant
3. Low VIII. FVIII carried by VWF - therefore if VWF low - FVIII low
4. Low VWF levels -> VWD
Case 3 contd.
What is the diagnosis? How would you manage this woman?
1. Treat anaemia
2. Treat menorrhagia
OCP
Tranexamic Acid
Mirena coil
3. Correct VWF
DDAVP
Rarely VWF-containing concentrates
Case 4 A 23-year-old woman with no past medical history of note
is admitted with a massive haematemesis. She is resuscitated with colloids and 12 units of red cells. Endoscopy reveals a Mallory-Weiss tear.
Following resuscitation a clotting screen is performed which shows:
Hb 8.4g/dl Platelets 56 x 109/L PT 45s APTT 98s Thrombin time: >60s Fibrinogen: 0.3g/L
Case 4 contd. What would explain these findings on coagulation testing? How would you manage these abnormalities?
1. Dilutional coagulopathy Resuscitation with colloids/concentrated red cells but no clotting factors/platelets
Could also be DIC - may complicate massive blood transfusion
2. Problems compounded by
acidosis/hypothermia and hypocalcaemia
3. FFP/Platelets/Fibrinogen Blood warmer Calcium if necessary
Case 5 A 67-year-old woman on warfarin for atrial
fibrillation is admitted with a major GI bleed. Her INR is 12.8 1. How would you manage this patient? 2. What questions might you ask that would be
relevant? 3. How does warfarin work and how do we
monitor it?
1. Needs rapid reversal of OACs with Octaplex or Beriplex [Prothrombin Complex concentrates [PCCs] + Vitamin K.
2. New drugs/confusion re. dose/intentional overdose
3. Vitamin K antagonist/INR
Case 6 A 48-year-old publican is investigated for easy bruising and
found to have the following profile: Hb 9.4g/dl Platelets 95 x 109/L PT: 23s APTT: 54s Thrombin time: 21s Fibrinogen: 1.2g/L What would explain these abnormalities? Why do these changes occur?
1. Consistent with liver disease
2. ↓ hepatic synthesis clotting factors
↓ bile production so ↓ VK absorption
Hypersplenism
Acquired platelet disorder
Low grade DIC
Hyperfibrinolysis
Case 7 A 23-year-old woman is seen in A & E with a
suspected proximal DVT What are the possible risk factors for the development
of a DVT What tests would you perform? How would you manage her?
1. OCP/BMI/FH/Pregnancy/recent surgery/malignancy/immobilisation
2. Wells Score/D-dimer [Exclude not confirm] – FBC/Renal & LFTs/PT/APTT Doppler leg
3. LMWH and then OACs – duration of treatment relates to presence or absence of any risk factors
VTE: Risk of Recurrence
Case 8 A 68-year-old woman is
admitted for a right hemicolectomy
What measures would you
take to reduce her risk of developing a DVT?
1. TED stockings
2. LMHW
3. Early mobilisation
Case 9 An 19-year-old man presents to his GP with purpura and
bruising. Previously well and no PMH/FH of note Hb 13.4g/dl Platelets 5 x 109/L WCC 6.8 x 109/L [Normal differential] Diagnosis? Further Tests? Management?
1. Severe Thrombocytopaenia
2. ? Drug induced
3. ? Viral
3. ? ITP
4. Repeat FBC + film
ANA
APS Screen
HIV and viral screen