Blood cells, clotting disorders and VTE

Question 1

What are the different types of blood cells?

Answer 1

Blood is broadly speaking composed of red blood cells (erythrocytes), platelets, white blood cells (leukocytes) and plasma (60%). White blood cells can be further divided into granulocytes (basophils, eosinophils, neutrophils), lymphocytes and monocytes.

Question 2

What are reticulocytes?

Answer 2

Reticulocytes are newly formed erythrocytes, so therefore an increased reticulocytes count indicates that erythrocyte production has increased. They retain a small amount of RNA and their lifespan is very short, which both provide information on the activity of the bone marrow.
Erythrocytes do not have a nucleus as they need volume to carry oxygen. Erythrocytes have a life-span of only 120 days

Question 3

What is erythropoiesis?

Answer 3

The production of erythrocytes from erythroblasts.

Question 4

What are the different types of leukocytes?

Answer 4

Leukocytes (WBC’s) are the cells of the immune system that are involved in protecting the body against infections disease and can be divided into:
– Granulocytes (Neutrophils, Eosinophils, Basophils)
– Monocytes
– Lymphocytes

Question 5

Describe neutrophils

- what causes and increase/decrease?

Answer 5

1) Neutrophils
– Normally make up 40-75% of all WBC’s
– First line of defence against all infections and act by phagocytosing invading organisms and presenting antigens to the immune system
– They have segmented nuclei and their cytoplasm is full of pinky-purple intracellular granules
– Short lived

Neutrophilia (↑) = bacterial infections, inflammation (e.g. MI), myeloproliferative disorders, drugs (steroids), disseminated malignancy, stress (trauma, surgery, burns, haemorrhage, seizure)

Neutropenia (↓) = viral infections, drugs (post-chemotherapy, cytotoxic agents, Carbimazole), severe sepsis, neutrophil antibodies (SLE, haemolytic anaemia), hypersplenism, bone marrow failure (decreased production)

Question 6

Describe Eosinophils - Causes of increase?

Answer 6

– Normally make up 1-6% of WBC’s
– Specifically act against multicellular parasites e.g. worms by dissolving their cell surfaces
– Are also involved in IgE-mediated allergic disorders e.g. asthma
– They have bilobed nuclei and intracellular granules which stain brick red with eosin. The pre-formed granules are released to destroy parasites.

Eosinophilia (↑) = drug reactions (e.g. with erythema multiforme), allergies (Asthma, atopy), parasitic infections (esp. helminths), skin disease (eczema, psoriasis, dermatitis)

Question 7

Describe basophils - what causes an increase?

Answer 7

– Normally make up 0-1% of WBC’s
– Circulating counterparts of tissue mast cells and although unknown, they probably have roles in inflammation, parasitic infections and allergic reactions
– They have bilobed nuclei and large darkly staining intracellular granules
– Granules contain heparin which prevents clotting
– Granules contain histamine which cause allergic reactions

Basophilia (↑): myeloproliferative disease, viral infections, IgE-mediated hypersensitivity reactions (urticaria, hypothyroidism) and inflammatory disorders (Rheumatoid arthritis, ulcerative colitis)

Question 8

Describe monocytes - what causes an increase?

Answer 8

– Normally make up 2-10% of WBC’s
– Are produced in the bone marrow and travel in the bloodstream to their target tissues, where they become macrophages.
– They have roles in phagocytosis, antigen presentation and cytokine production
– They are large cells with few granules and horseshoe-shaped nuclei

Monocytosis (↑): post-chemo- or radiotherapy, chronic infections (malaria, TB, brucellosis), malignancy disease (AML, Hodgkin’s disease), myelodysplasia

Question 9

Describe lymphocytes - what causes and increase and decrease?

Answer 9

– Normally make up 20-45% of all WBC’s
– Transform to lymphoblast’s and proliferate when infection is present
– There are three main subtypes of lymphocytes: B cells, T cells and natural killer (NK) cells
– B cells and T cells make up the majority of the lymphocyte population. They are small cells with large round nuclei, scanty blue-ish cytoplasm and no granules
– NK cells are a larger, more primitive lymphocyte subtype which do contain some granules.

1) B-Lymphocytes
o B cells represent about 25% of the total lymphocyte population
o Important B cell surface markers include CD19, CD20 and CD21, as well as MHC II
o They are essential for humoral immunity, also known as the antibody-mediated immune response
o Plasma cells are mature B cells which secrete antibodies, which recognise specific foreign antigens and bind to them or destroy them
o Memory B cells “remember” the offending foreign antigens to allow the immune system to mount a quicker antibody response to any subsequent infections

2) T-Lymphocytes
o T cells represent about 70% of the total lymphocyte population
o All T cells express CD3 on their surfaces, along with T cell receptors(TCRs) which recognise specific antigens presented in an MHC I or MHC II molecule
o There are numerous different T cell subtypes with different roles, which each have their own identifiable surface markers
o Helper T cells (CD4): facilitate the activation of the immune response and stimulate division and differentiation of various effector cells
o Cytotoxic T cells (CD8): Aka killer or effector T cells, provide cell-mediated immunity by targeting and killing infected cells
o Regulatory T cells (CD25 + FOXP3): Aka suppressor T cells, play a vital role in limiting the immune response to prevent excessive damage to tissues and organs
o Memory T cells (CD62 + CCR7): “remember” what has happened to allow the immune system to mount a faster, more effective response should the offending organism be foolish enough to return

3) Natural killer cells
o NK cells represent about 5% of the total lymphocyte population
o NK cells are a larger, primitive lymphocyte subtype with granules in their cytoplasm
o They express CD15 and CD56, and a large proportion of them also express CD8
o NK cells actually form part of both the innate and adaptive immune systems and are able to destroy pathogens and infected cells without the need for prior activation by specific antigens. They are also particularly important in viral immunity and tumour rejection.

Lymphocytosis (↑): acute viral infections, chronic infections (TB, brucella, hepatitis, syphilis), leukaemia’s or lymphomas

Lymphopenia (↓): steroid therapy, SLE, uraemia, legionnaire’s disease, HIV infection, marrow infiltration, post chemotherapy or radiotherapy.

Question 10

What are the 13 different clotting factors?

Answer 10

There are 13 clotting factors – labelled I-XIII, but clotting number VI is absent so in total there are only 12 factors to discuss and know.

Factor I = Fibrinogen
• Source = liver*.

Factor II = Prothrombin
• Source = liver*.
• Prothrombin splits into a number of small proteins e.g. thrombin (fibrinogen –> fibrin)

Factor III= Thromboplastin/Tissue factors
•Source = platelets/endothelium.
• Factor III is involved in the initiation of the intrinsic pathway and is always release when there is damage to the blood vessel

Factor IV = Calcium
• Source= bone and from absorption into the gastrointestinal tract.
• Calcium is involved in almost all the reactions of the intrinsic and extrinsic pathways,

Factor V = Labile factor/proaccelerin
• Source = liver and platelets

Factor VI = xxxxxx

Factor VII = Proconvertin/ serum prothrombin conversion accelerator (SPCA)
• Source = liver*.

Factor VIII = Anti-haemophilic factor A
• Source = endothelium

Factor IX = Christmas factor/ anti-haemophilic factor B
• Source = liver*.

Factor X = Stuart factor
• Source = liver*.

Factor XI = Plasma thromboplastin antecedent (PTA)
• Source = liver*.

Factor XII = Hageman factor
• Source = liver*.

Factor XIII = fibrin stabilising factor

*Liver = liver disease will affect the production of fibrinogen and consequently affect the coagulation pathway.

Question 11

Explain coagulation cascade?

Answer 11

When endothelial injury occurs, the cells no longer have a complete barrier, and this allows blood to haemorrhage out. The blood has a method to contain the blood and this is called coagulation.

Firstly, platelets within the blood vessel will accumulate at the site of injury to from an initial ‘PLATELET PLUG’. This plug is not solid enough on its own, so a second mechanism is required to strength the platelet plug. The strength is supplied by fibrin strands.

The fibrin strands are made of fibrin subunits and these subunits have a natural affinity for themselves, so that when they come together they form a strong strand. Obviously, the body doesn’t want or need fibrin stands in the absence of endothelial injury, so fibrin strands do not exist in the blood normally. Fibrinogen exists in the blood normally and fibrinogen has the fibrin subunit but with an additional section that prevents aggregation and fibrin strand formation.

When endothelial injury occurs, the blood is exposed to new proteins and the endothelial cells itself will release new proteins into the blood. These proteins eventually cause the conversion of fibrinogen to fibrin. Thrombin converts fibrinogen to fibrin. Thrombin is activated from its inactive form Prothrombin.

Coagulation pathway story:
Start counting back from 12… XII  XI… but because you’re not very good at counting you forget 10… XI  IX… and then you remember 10… XI  X. 10 is very important because it is involved in the formation of thrombin (also known as II) which then forms fibrin (also known as I). It makes sense that fibrin is I as fibrin is the main goal, and thrombin is the 2nd most important. X works well with V because they’re multiples of 5, and IX likes to work with VIII because they’re normally together.

XII, XI, [IX + VIII], [X + V] make up the intrinsic system.

It is important to note that XII is not becoming XI. The arrows show that XII, once activated to XIIa will convert inactive XI to active XIa. Xia acts as a catalyst to activate IX to IXa.

The extrinsic pathway also causes activation of X. in the extrinsic pathway X is activated by VII, which is activated by III (also known as tissue factor). The extrinsic pathway is described as the ‘spark’ that is brought on by the endothelial injury, whereas the intrinsic pathway is the hard worker. So, the endothelial injury sparks the extrinsic system: III activates VII which activates a small amount of X. X activates a small amount of II and it is II that stimulates the intrinsic pathway. II activates the odd numbers starting from 5: V, VII, VIII (not 9), XI, XIII. XIII is involved in forming cross links between the fibrin strands to form a mesh. Thrombin (II) basically has a positive feedback to increase its own production.

Without a negative feedback system, this coagulation cascade would continue and continue. Therefore, there are a few negative feedback situations that also occur!

1. Thrombin also produces plasmin from plasminogen. Plasmin acts on the fibrin mesh networks to break them apart.
2. Thrombin stimulated the production of anti-thrombin III. Anti-thrombin decreases the amount of thrombin produced from Prothrombin. It also impeded the production of activated X from X.

Question 12

How is vitamin K related to the clotting cascae?

Answer 12

Vitamin K is as a cofactor for an enzyme that enables specific proteins to bind calcium. The ability to bind calcium ions (Ca2+) is required for the activation of vitamin K-dependent clotting factors (II, VII, IX, X, Protein C and Protein S).
Vitamin K-dependent clotting factors are synthesized in the liver. Consequently, severe liver disease results in lower blood levels of vitamin K-dependent clotting factors and an increased risk of uncontrolled bleeding.

Question 13

How is the coagulation cascade regualted?

Answer 13

1. Protein C
   Protein C is a major physiological anticoagulant. It is a vitamin K-dependent serine protease enzyme that is activated by thrombin into activated protein C (APC). The activated form, along with protein S and a phospholipid as cofactors, degrades Factor V and Factor VIII.
2. Antithrombin
   Antithrombin is a serine protease inhibitor (serpin) that degrades the serine proteases: thrombin, Factor IX, Factor Xa, Factor XI, and Factor XII. It is constantly active, but its adhesion to these factors is increased by the presence of heparan sulfate (a glycosaminoglycan) or the administration of heparins
3. Tissue factor pathway inhibitor (TFPI)
   Tissue factor pathway inhibitor (TFPI) limits the action of tissue factor (TF). It also inhibits excessive TF-mediated activation of FVII and FX.
4. Plasmin
   Plasmin is generated by proteolytic cleavage of plasminogen, a plasma protein synthesized in the liver. This cleavage is catalyzed by tissue plasminogen activator (t-PA), which is synthesized and secreted by endothelium. Plasmin proteolytically cleaves fibrin into fibrin degradation products that inhibit excessive fibrin formation

Question 14

What type of bleeding disorders are there?

Answer 14

1)Vascular defects
• Congenital: Osler-Weber-Rendu syndrome, connective tissue disease (e.g. Ehler-danlos syndrome)
• Acquired: senile purpura, infection (e.g. meningococcal, measles, dengue fever), steroids, scurvy, Henoch- Schonlein purpura (IgA abnormality), painful bruising syndrome

2) Platelet disorder
• Decreased marrow production: aplastic anaemia, megaloblastic anaemia, marrow infiltration (leukaemia, myeloma), marrow suppression
•Excess destruction
o Immune: Immune thrombocytopenic purpura, SLE, drugs (heparin)
o Non-autoimmune: thrombotic thrombocytopenic purpura, or HUS
•Poorly functioning platelets: seen in myeloproliferative disease, NSAIDs, and urea increase.

3) Coagulation disorders
•Congenital: haemophilia (A, B, C), von Willebrand’s disease
•Acquired: anticoagulants, liver disease (reduced clotting factors produced), DIC, vitamin K deficiency

Question 15

How do you investigate bleeding disorders?

Answer 15

1) Prothrombin Time (PT): thromboplastin is added to test the extrinsic system. PT is expressed as a ration compared to control – International normalised ratio (INR), normal rate = 0.9-1.2. It tests for abnormalities in factors I, II, X + V, VII
• Prolonged by: Warfarin, vitamin K deficiency, liver disease, disseminated intravascular coagulation (DIC)

2) Activated partial thromboplastin time (APTT): Kaolin is added to test the intrinsic system. Tests for abnormalities in I, II, X + V, IX, XI, XII. Normal range = 35-45seconds.
•Prolonged by: heparin treatment, haemophilia, disseminated intravascular coagulation (DIC) and liver disease.

3) Thrombin time: thrombin is added to plasma to convert fibrinogen to fibrin. Normal range: 10-15 s3conds
• Prolonged by: heparin treatment and DIC

4) D-dimers are a fibrin degradation product, released from cross-linked fibrin during fibrinolysis. This occurs during DIC or in the presence of venous thromboembolism (DVT /PE). D-dimers may also be raised in inflammation (e.g. with infection or malignancy)

5) Bleeding time tests haemostasis. It is done by making two small incisions into the skin of the forearm. Normal time to haemostasis = <10mins.
• Raised in von Willebrand’s disease, platelet disorder and if on aspirin

Question 16

What is haemophilia and how does it present?

Answer 16

Haemophilia is a medical condition in which the ability of the blood to clot is severely reduced, causing the sufferer to bleed severely from even a slight injury. The condition is typically caused by a hereditary lack of coagulation factors (VIII or IX).

There are 2 types of haemophilia – haemophilia A (reduction in factor VIII) and haemophilia B (reduction in factor IX). Both produce the same clinical disease and can be classified in the same way

Factor level (<1) = Severe, spontaneous bleeding, 1-2x per week, often occurs around the joint.

Factor level (1-5), moderative, slight injury, once monthly.

Factor level (>5) = Mild, bleeding occurs only on trauma.

The basic principles for treatment are the same for both types of haemophilia. It is very important to treat these type of patients early as they need to be fast tracked into A&E. Don’t wait for clinical signs to develop -just treat. Ensure you take care of the veins, avoid drugs like aspirin and start early home therapy.

Question 17

How do you treat haemophilia?

Answer 17

Initially treatment should be RICE – Rest, immobilise, cool and elevate
Haemophilia A treatment
• Need to replace levels of factor VIII.
• Factor VIII has a half-life of 8 hours so needs to be given 1-3 x daily
• Amount needed is calculated by: [Rise in factor VIII x weight (kg)] / 2
• Desmopressin (DDAVP) can also be used. It releases stored factor VIII and raises VIII levels by 2-3 time. Can be given SC, IV or IN.
• Tranexamic acid can also be used. It is an anti-fibrinolytic which is given orally.

Haemophilia B treatment
• Need to replace levels of factor IX.
• Factor IX has a half-life of 18-24 hours so need to be given once daily
• Amount needed is calculated by: [Rise in factor IX x weight (kg)]
• Tranexamic acid can also be used. It is an anti-fibrinolytic which is given orally.

There are two types of long-term treatments for haemophilia. The first is known as ‘demand’ treatment but is no longer performed in the UK. It doesn’t prevent blood getting into joints, it doesn’t prevent morbidity and it may not be the cheap option in the long term. The second treatment is known as prophylaxis treatment.

Question 18

How is haemophilia prophylactically treated?

Answer 18

Primary treatment given between 18mths and 3 years.

Secondary treatment given after 3 joint bleeds

Factor IX is given 2 times per week

Factor VIII is given alternate days but still often 3x per week

Prophylaxis treatment is very expensive but very effective.

Question 19

What is von Willebrand’s disease?

Answer 19

Von Willebrand’s disease is the commonest coagulopathy that effects 0.5% of the population. It causes mucocutaneous bleeding and causes approx. 15% of the cases of menorrhagia. There are 3 types and it is difficult to diagnosis this disease.

This is usually autosomal dominant.
• Type 1 – reduced amount of normal vW protein (quantitative deficiency)
• Type 2 – abnormal vW protein (IIb overactive) (qualitative deficiency)
• Type 3 – little or no vW

Types 1 and 2 are differentiated by using the ratio of vWF activity: vWF antigen. If the ratio is >0.6 = Type 1 and if <0.6 = type 2

Question 20

How do you test for von willebrand’s disease

Answer 20

1. Factor VIII because the vW is the factor VIII carrying protein.
2. Von Willebrand antigen
3. Von Willebrand activity

Question 21

Describe type 1 vW disease?

Answer 21

• Common mild disease
• Bruising/Mucosal Bleeding
• Menorrhagia
• Caution in operations – dental extractions

Treatment: DDAVP + Tranexamic acid (watch for diminishing returns in major surgery)

Question 22

Describe type II vW disease?

Answer 22

Type 2 is as for type 1, but watch for type 2b:
• Overactive vW protein
• Can result in thrombocytopenia
• Avoid DDAVP (will release vW from stores)
• Use vWF concentrate

Question 23

Describe type III vW disease?

Answer 23

• Severe illness
• Serious mucosal bleeding
• Operative treatment will cause severe bleeding

Question 24

What is a venous thromboembolism?

Answer 24

DVT and PE are both forms of venous thromboembolism (VTE). The distinction is not very useful as 50% of DVT patients had silent PE on lung scan and most PE patients without obvious DVT in fact had DVT on imaging.

Most VTE develop in the deep veins of the leg. Normally contraction of the calf muscles squeezes bloods up the deep veins of the leg and the internal venous valves prevent it flooding back. However, in disease states such as varicose veins this does not work efficiently and there is back wash of blood, the veins bulge and blood pools in the deep veins.

VTE is common, dangerous and costly to the NHS. It is estimated to cause 25,000 deaths per year (more than the annual death toll from RTA, HIV and even breast cancer). VTE is the major avoidable cause of death in modern medicine. VTE consists of 66% DVT and 33% PE. VTE is the cause of 10% of hospital deaths; most are sudden and unexpected

Question 25

Describe virchow’s triad?

Answer 25

Virchow’s triad describes the 3 primary abnormalities that lead to the formation of a thrombus (blood clot).
A thrombus is basically a blood clot, whereas an embolus is any detached intravascular solid, liquid or gas that is carried by the blood to a site that is different from its origin. A thrombus can become an embolus, a thrombo-embolus, when a piece of the original blood clot breaks off and travels in the blood stream to a different site.

Virchow’s triangle is made of 3 factors:

1. Endothelial injury
   - Endothelial damage can be caused by Hypertension, Infection, Toxins, Metabolic disturbance e.g. hyperlipidaemia, high cholesterol
   - Essentially there is loss of endothelium which results in activation of platelet adhesion, tissue factor and coagulation cascade activation which result in the formation of a fibrin clot.
2. Turbulence or stasis of blood flow
   - Turbulent blood flow is more chaotic than laminar flow.
   - It is not only caused by endothelial injury but can also cause endothelial injury.
   - These pockets of turbulence lead to stasis (slow flowing or stagnant blood)
   - the reduction of laminar flow means that platelets will come into contact with the endothelial lining of the blood vessel. The turbulence of blood and increase contact time between endothelium and platelets actually activated the platelets to start the coagulation cascade.
3. Hypercoagulability (increased tendency to clot)
   - A disruption to the coagulation cascade predisposes to a thrombus formation. These causes can be divided into: Primary/innate causes (e.g. genetic conditions) or Secondary/ acquired causes (e.g. development of a heart arrhythmia (AF))

Question 26

What is the fate of a thrombus?

Answer 26

1. Dissolution through the process of fibrinolysis
2. Propagation = continues to grow by accumulating platelets and clotting factors
3. Recanalization = thrombus reorganises and re-canalises, ingrowth of smooth muscle cells and endothelium into a fibrin rich thrombus. If this continues, blood flow can be diverted through the thrombus to prevent ischaemia.
4. Embolization = embolus forms from the thrombus

Question 27

How do you prevent VTE?

Answer 27

Risk assess each patient
Early ambulation for all

1. Mechanical intervention:
   • Anti-embolism stockings (AES)
   • Intermittent pneumatic compression sleeves (IPC)
2. Pharmacological interventions
   • Low dose low molecular weight heparin (SC) – LMWH e.g. Dalteparin, enoxaparin
   •Low dose unfractionated heparin (IV) – UFH
   •Direct anti-Xa and anti-thrombin drugs (Oral) – DOACs

Question 28

What are the benefits and downfalls of VTE prophylaxis?

Answer 28

Mechanical intervention:
 Cheap
Do not affect the coagulation system
 Poor compliance with optimum fitting
 May exacerbate pre-existing arterial insufficiency
 Less effective than pharmacological management

Pharmacological interventions:
 Effective
 Expensive
 Risk of bleeding
Allergies and Heparin Induced Thrombocytopenia and Thrombosis (HITT)
 Do not use warfarin as the intensity of anticoagulation is less predictable and erratic bleeding risk higher than heparin or DOAC

Question 29

How is a VTE managed?

Answer 29

Once suspected according to clinical signs and symptoms (Wells scores) then treat at once.
Do not investigate first unless this can be done within 1 hour for PE or 4 hours for DVT
Use Heparin – usually LMWH but sometimes particularly post-op it may be preferred to use UFH because UFH can be immediately reversed (Protamine Sulphate) or just stopped (T1/2 @20 minutes) if post-op bleeding or redo surgery required
At the same time as starting heparin begin oral warfarin (except in some post-op patients. Warfarin takes 48 to 72 hours to reach its therapeutic range at which time the heparin can be discontinued

A thrombus is a blood clot within the body. An embolus is some material which is transported in the blood stream and lodges in a blood vessel at a different site. An embolus can be gaseous, e.g. an air bubble, or solid, e.g. part of a thrombus. When it impedes or blocks blood flow in the artery it causes an embolism, the consequences of which are infarction of the tissue supplied by the artery. The bigger the embolus the bigger the artery it blocks and the bigger the area of infarction.

Question 30

How does a DVT present?

Answer 30

DVTs occur in 25-50% of surgical patients and many non-surgical patients. Therefore, all hospital inpatient should be assessed for DVT/PE risk and offered prophylaxis.

DVT presentation:
A unilateral, swollen, painful leg, heavy ache in the affected area, warm skin, red skin.
An examination of a DVT would show:
• Warm, swollen leg.
• Tenderness in the calf – worse with dorsiflexion of the ankle (Homan’s sign).
• Calf circumference greater than 3 cm compared with unaffected leg. To ensure you are comparing like for like – take a tape measure and make a mark at 10cm from tibial tuberosity on each leg. Then use this mark to measure circumference.
* Other similar presentations: Cellulitis (infection of the skin of the leg), a ruptured baker’s cyst, muscle haematoma

Question 31

What are the causes /risk factors for DVT?

Answer 31

More common over the age of 40
History of DVT or pulmonary embolism

Family history of blood clots

/Inactive for long periods – such as after an operation or during a long journey

Blood vessel damage – a damaged blood vessel wall can result in the formation of a blood clot

Certain conditions or treatments that cause your blood to clot more easily than normal e.g. cancer (including chemotherapy and radiotherapy treatment), heart and lung disease, thrombophilia and Hughes syndrome

Pregnancy – your blood also clots more easily during pregnancy

Overweight or obese (BMI >30)

Use of the combined contraceptive pill or hormone replacement therapy (HRT)

Diabetes

Smoking
Atherosclerotic disease
Varicose veins/phlebitis history

Question 32

How do you investigate a DVT?

Answer 32

Calculate Wells score
If Wells score is <1 then DVT is unlikely, but you still need to perform a D-dimer
oNegative D-dimer and low clinical probability Wells score = exclude DVT
o Positive D-Dimer = USS of leg

If Well score is >2, DVT is likely. You need to perform a D-dimer and USS.
o Positive USS = Treat as DVT
o Negative USS = repeat 1 week later to catch early but propagating DVT’s.

Question 33

How do you calculate the wells score for DVT

Answer 33

Active cancer (treatment within the last 6 months or palliative)

Paralysis, paresis or recent plaster immobilization of leg

Recently bedridden for >3days or major surgery in last 12wks

Local tenderness along distribution of deep venous system

Entire leg swollen

Calf swelling >3cm compared with asymptomatic leg

Pitting oedema

Collateral superficial veins (non-varicose

Previously documented DVT

Alternative diagnosis at least as likely as DVT

Question 34

How do you treat a DVT?

Answer 34

1) LMWH (e.g. enoxaparin) or fondaparinux.

2) Start warfarin simultaneously (warfarin has no effects for the first 2-3 days).

Question 35

What are the signs and symptoms of a PE?

Answer 35

Symptoms and signs:
• Sudden onset of pleuritic chest pain
• Acute breathlessness
•Haemoptysis/ coughing
• Syncope
•Dizziness

Signs: 
• Tachypnoea + acute breathlessness
• Pyrexia
• Cyanosis
• Tachycardia
• Hypotension
• Raised JVP
• Pleural rub
• Pleural effusion 
• DVT (less likely if the DVT is present below the knee)

Question 36

How do you diagnose a PE?

Answer 36

Bloods: FBC, U& E, baseline clotting, D-dimer

ABG: may show decreased O2 and decreased CO2

CXR: may be normal or show oligaemia of affected segment, dilated pulmonary artery, linear atelectasis, small pleural effusion, wedge-shaped opacities or cavitation

ECG: may be normal or show tachycardia, RBBB, right ventricular strain (inverted T in V1-V4). The class SI, QIII, TIII pattern is rare.

Question 37

How is a PE managed?

Answer 37

Calculate wells score
If Wells score is low then PE is unlikely, but still do a d-dimer
- Negative D-dimer and low clinical probability Wells score = exclude PE
- Positive D-Dimer = imaging is required

If Well score is high a PE is likely. Imaging is required – do a CTPA

Question 38

How do you manage a massive PE?

Answer 38

1. Oxygen if hypoxic (10-15l/min)
2. IV Morphine (5-10mg) with anti-emetic if distressed or in pain
3. If critically ill with massive PE (i.e. per-arrest) consider immediate thrombolysis (bolus alteplase)
4. IV access and start heparin (LMWH – tinzaparin or UFH)
5. Measure Systolic BP
   a) <90mmHg = Start rapid colloid infusion and get ICU input. If BP is still decreasing, give dobutamine. If BP is still low, consider noradrenaline. If still low after 30-60mins = clinically definite PE and no contraindications, consider thrombolysis
   b) >90mmHg = start warfarin.