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