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75 Cards in this Set

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  • Back

What is Low molecular weight heparin, what are some examples and why is it used in preference to heparin


- given subcutaneously

- e.g. dalteparin, enoxaparin, tinzaparin

- molecular weight ~5,000 Daltons

- inactivates factor Xa (but not thrombin)

- half life is 2-4 fold longer than standard heparin, and response is more predictable and so only needs to given once or twice daily, and no laboratory monitoring is usually required.

- has replaced unfractionated heparin as the preferred option in the prevention and treatment of venous thromboembolism and in acute coronary syndrome

When would you use LMWH over UFH, and vice versa?

- has replaced unfractionated heparin as the preferred option in the prevention and treatment of venous thromboembolism and in acute coronary syndrome

- it accumulates in renal failure: lower doses are used for prophylaxis or unfractionated heparin for therapeutic doses

What is the contraindication of LMWH?

- it accumulates in renal failure: lower doses are used for prophylaxis or unfractionated heparin for therapeutic doses

What is unfractionated heparin?

- IV or subcutaneously

- ~13,000 daltons

- a glycosaminoglycan which binds antithrombin (an endogenous inhibitor of coagulation), increasing its ability to inhibit thrombin, factor Xa and IXa

- rapid onset and has a short half life

- monitor and adjust dose with APTT

What are the side effects for LMWH and unfractionated heparin?

- increased risk of bleeding (e.g. at operative site, gastrointestinal, intracranial)

- heparin induced thrombocytopenia

- osteoporosis with long-term use

- heparin induced thrombocytopenia and osteoporosis are less common with LMWH than unfractionated heparin

- beware hyperkalaemia

What are the contraindications of LMWH and unfractionated heparin?

- bleeding disorders

- platelets <60 x10^9/L

- previous heparin induced thrombocytopenia

- peptic ulcer

- cerebral haemorrhage

- severe hypertension

- neurosurgery

What is warfarin ?

- warfarin inhibits the reductase enzyme responsible for regenerating the active form of vitamin K, producing a state analogous to it K deficiency

What are the contraindications of warfarin use?

- peptic ulcer

- bleeding disorders

- severe hypertension

- pregnancy (teratogenic)

Use with caution in the elderly and those with past GI bleeds

What is fondaparinux?

- a pentasaccharide Xa inhibitor and may be used in place of LMWH for prophylaxis in certain situations

What are rivaroxaban and apixaban?

Factor Xa inhibitors

- do not need monitoring

What is dabigatran?

direct thrombin inhibitors

- do not need monitoring

What is the target INR of warfarin use


- unless antiphospholipid (Hughes’) syndrome (recurrent thromboses, miscarriages, migraine thrombocytopenia) , in which INR must be over 3

How do you treat venous thromboembolism?

LMWH or UFH are used initially, and warfarin is given in combination usually from day 1

- heparin should be continued until INR has reached target therapeutic range (2-3) and until day 5, as warfarin has an initial protrhombotic effect

What is Hodgkin’s lymphoma characterised by?

Hodgkin’s lymphoma is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell

What ages typically tend to be affected by Hodgkin’s lymphoma

bimodal age distribution

- early 20s

- 70s

What is the histological classification of Hodgkin’s lymphoma?

nodular sclerosing

- most common; around 70%

- good prognosis

- more common in women

- associated with lacunar cells

mixed cellularity

- around 20%

- good prognosis

- associated with a large number of Reed-Sternberg cells

lymphocyte predominant

- around 5%

- best prognosis

lymphocyte depleted

- rare

- worst prognosis

What factors are associated with a poor prognosis?

- lymphocyte depleted Hodgkin’s lymphoma

B symptoms also imply a poor prognosis

- weight loss >10% in last 6 months

- fever >38

- night sweats

Other factors:

- age >45 years

- stage IV disease

- haemoglobin <10.5 g/dl

- lymphocyte count <600 or <8%

- male

-albumin >40 g/l

- white blood count >15,000

What are the B symptoms?

- weight loss >10% in last 6 months

- fever >38

- night sweats

What type of Hodgkin’s lymphoma is associated with the best prognosis?

Which is associated with the worst prognosis?

best = lymphocyte predominant

worst = lymphocyte depleted

What causes an increase neutrophils? (neutrophilic)

- bacterial infections

- inflammation e.g. myocardial infraction, polyarteritis nodosa

- myeloproliferative disorders (polycythaemia rubra vera, CML, essential thrombocythaemia, myelofibrosis)

- drugs (steroids)

- disseminated malignancy

- stress e.g. trauma, surgery, burns, haemorrhage, seizures

What causes a decrease in neutrophils? (neutropenia)

- viral infections

- drugs e.g. post chemotherapy, cytotoxic agents, carbimazole (used to treat hyperthyroidism), sulfonamide (antibacterial)

- severe sepsis

- neutrophil antibodies (SLE, haemolytic anaemia) - as incr. destruction

- hypersplenism e.g. Felty’s syndrome

- Bone marrow failure - as decr. production

What causes an increase in lymphocytes? (lymphocytosis)

Increased in:

- acute viral infections

- chronic infections e.g. TB, Brucella, hepatitis, syphilis

- Leukaemias and lymphomas, especially chronic lymphocytic leukaemia

Large numbers of abnormal (‘atypical’) lymphocytes are characteristically seen with EBV infection: these are T cells reacting against EBV-infected B cells. They have a large amount of clearish cytoplasm with a blue rim that flows around neighbouring RBCs

What causes a decrease in lymphocytes (i.e. lymphopenia)?

- steroid therapy


- uraemia

- Legionnaire’s disease

- HIV infection

- marrow infiltration

- post chemotherapy or radiotherapy

What causes an increase in eosinophils? (i.e. eosinophilia)

- drug reactions e.g. with erythema multiform

- allergies: asthma, atopy

- parasitic infections (especially invasive helminths)

- skin disease - especially pemphigus, eczema, psoriasis, dermatitis herpetiformis

Also seen in malignant disease (including lymphomas and eosinophilic leukaemia), PAN, adrenal insufficiency, irradiation, Loffler’s syndrome, and during the convalescent phase of any infection

- also the hyepereosinophilic syndrome in which an increased eosinophil count for >6 weeks leads to end-organ damage

What causes an increase in monocytes (i.e. monocytosis)

- post chemo-or radiotherapy

- chronic infections e.g. malaria, TB, brucellosis, protozoa

- malignant disease (incl. acute myeloid leukaemia and Hodgkin’s disease)

- myelodysplasia

What causes an increase in basophils?

Increased in :

- myeloproliferative disease

- viral infections

- IgE mediated hypersenstivity reactions (e.g. urticaria, hypothyroidism) and

- inflammatory disorders e.g. UC, rheumatoid arthritis

What is the mutation that causes sickle cell disease and how is it inherited?

substitution of glutamate by valine in position 6 of the beta globin gene

- autosomal recessive; mendelian mode of inheritance

- carrier status = asymptomatic

What is the benefit of being a sickle cell carrier?

protection against falciparum malaria

What is the problem with HbS (sickle cell haemoglobin)?

The chains polymerise which leads to sickling.

Problems from this are:

- infarction/vaso-occlusion

- haemolysis

What are the precipitating factors to polymerisation of sickle cell haemoglobin chains?

- hypoxia

- HbS concentration/dehydration

- acidosis

What is the mechanism of sickle cell induced vasculopathy?

- intravascular sickling (i.e. polymerisation of sickle cell haemoglobin chains)

- leads to occlusion of post-capillary venules (vaso-occlusion)

- this leads to endothelial damage

- reperfusion of this damaged endothelium leads to ischaemia reperfusion injury

- this leads to an alteration of adhesion molecules

- activation of coagulation cascade

- and NO depletion

How do you diagnose sickle cell disease?


- family history

- recurrent pain

- leg ulcers

Laboratory (Haem/biochemical)

- anaemia

- haemolysis (high bilirubin, LDH, reticulocytes)

Blood film

Haemoglobin electrophoresis/sickle solubility test

sickle solubility test = put a testtube in front of some lines, if you can see lines = negative, if you cannot see lines = positive (i.e. so thick can’t see lines)

What are the Clinical Features of Sickle Cell Disease?



- stroke

- ‘silent’ cerebral infarcts


- Acute chest syndrome

- Chronic sickle lung disease


- Autoinfarction

- Risk of overwhelming sepsis

Aplastic crisis

- Due to Parvovirus B19 infection


- pulmonary hypertension

- systemic hypertension

- myocardial infarction


- hyposthenuria

- hyperfiltration

- proteinuria

- renal failure


- gall stones

- intrahepatic cholestasis


- avascular necrosis

- bone infarcts

Leg Ulcers



- vitreal haemorrhage

- retinopathy

What are the emergency presentations of sickle cell disease?


- acute painful crisis

- acute abdominal pain

- chronic pain


- sequestration

- aplastic crisis

- overwhelming sepsis

- acute chest syndrome

- acute neurological presentation

- fat embolism syndrome/Multi-organ failure

- renal impairment

- priapism (painful persistent erection)

- acute visual loss

What are the features of a painful sickle cell crisis?

- a vaso-occlusive crisis most commonly involves the back, legs, knees, arms, chest and abdomen.

The pain generally affects two or more sites. Bone pain tends to be bilateral and symmetric. An acute abdominal pain crisis often resembles an intra-abdominal process such as cholecystitis or appendicitis

- rapid onset of bone pain; bone marrow infarction

- variable severity and duration; hours to weeks

- fever, bone tenderness +/- swelling, hypertension, tachycardia, tachypnoea

What are the precipitating factors to a painful sickle cell crisis?

- infections

- skin cooling

- dehydration

- deoxygenation

- stress

most common sites - lumbar spine = 49%, abdominal = 32%, femur = 30%

What is the treatment of a sickle cell crisis?

1) adequate and prompt analgesia

deliver within 30 min from presentation; parenteral opiate analgesia often required; re-assess and repeat as necessary


- 02 saturation

- respiratory rate

- heart rate

- ? blood pressure

- temperature

- fluid intake

- analgesia use & pain score

- sedation/urinary retention/restlessness


- FBC + reticulocytes




- Group & save

- ?blood cultures

- ? CXR

What is acute chest syndrome?

all ages; commonest cause of death in sickle cell adults (25% of all deaths)

- 2nd most common cause of hospitalisation

definitions = acute illness, new infiltrate on CXR, respiratory symptoms

- HbSS>>HbSC, high Hb, low HbF


- infection

- pulmonary infarction - in situ sickling

- surgery/anaesthesia, pregnancy

- rib infarction, pulmonary sequestration, fat embolism

- increased risk of chronic lung disease

- increased risk of death

What is the pathophysiology of acute chest syndrome?

- hypoventilation, asthma, infection

- lead to hypoxia inflammation acidosis

- leads to vasocclusion within the pulmonary microvasculature (fat emboli and pulmonary thrombi also cause this)

- which leads to hypoxia inflammation acidosis

What may be the symptoms of acute chest syndrome?

The crisis is a common complication in sickle-cell patients and can be associated with one or more symptoms including fever, cough, excruciating pain, sputum production, shortness of breath, or low oxygen levels.

What is the difference in terms of reticulocytes of anaemia from destruction/loss and anaemia from low/no preduction?

anaemia from destruction/loss e.g. bleeding or haemolysis

- reticulocytes >2%

anaemia from low/no production e.g. aplastic anaemia

- reticulocytes 0%

What are the signs and symptoms of anaemia?


- yellowing (red in severe anaemia)


- paleness

- coldness

- yellowing


- shortness of breath


- weakness


- changed stool colour


- fatigue

- dizziness

- fainting

blood pressure

- low bp


- palpitations

- rapid heart rate

- chest pain

- angina

- heart attack


- enlargement

What are the causes of a microcytic anaemia?

normal MCV = 79-97

microcytic = low

RBC count

male 4.7 to 6.1 million cells/mcL

female 4.2 to 5.4 million cells/mcL

low or normal RBC:

- iron deficiency anaemia

- anaemia of chronic inflammation

- lead poisoning

- sideroblastic anaemia

high RBC:

- thalassaemias (alpha and beta thalassaemias; or combination with other haemoglobin abnormalities)

What are the causes of a normocytic anaemia?

normal MCV = 79-97

- haemolytic anaemias

- bone marrow disorders

- hypersplenism

- acute blood loss

- anaemias of chronic disease

What are the causes of a macrocytic anaemia?

normal MCV = 79-97

macrocytic = high

- vitamin B12 deficiency

- folic acid deficiency

- liver disease

- hypothyroidism

- reticulocytosis

In anaemia, what type of shift do you get on the haemoglobin saturation/2,3 DPG curve

right shift of 2,3 DPG curve as part of acute compensation

What are the acute compensation methods of anaemia?

1) right shift of 2,3 DPG curve

2) increased cardiac output (increase stroke volume or increase heart rate or increase both)

3) redistribution of blood flow

What is anaemia?

Reduced total number of RBC or Hbg or red cell mass

What are the chronic compensation mechanisms of chronic severe anaemia?

- chronic severe anaemia

- peripheral vasodilation

- decreased blood pressure

- increased neurohormones (catecholamines, RAA, natriuretic peptides, AVP)

- decreased renal blood flow; decreased GFR

- increased salt and water retention

- increase in extracellular volume; increase in plasma volume

- increase in work load; increase in LV mass; increase in LV remodelling; increase in LV dysfunction

- worsening heart failure

- chronic severe anaemia

Anemia causes a fall in systemic vascular resistance, attributable, in part, to the reduced viscosity of the blood and, in part, to nitric oxide-mediated vasodilation. The decrease in systemic vascular resistance reduces the blood pressure and causes activation of the baroreceptors (as it does in low-output CHF), which, in turn, activates the sympathetic, renin-angiotensin-aldosterone system and vasopressin systems, causing tachycardia and peripheral vasoconstriction and a decrease in renal blood flow and glomerular filtration rate. This leads to salt and water retention and an increase in extracellular and plasma volume. As a consequence, left ventricular dilation and hypertrophy can occur, with the net result being the production or worsening of CHF. As mentioned, the same mechanism is present in low-output CHF so that we have two diseases, anemia and CHF, with the same pathophysiology.

What is the management of anaemia?

- treat the cause

- balanced diet, education and health support

- human recombinant erythropoietin

- blood transfusion (only when there is no other treatment)

What is the length of warfarin treatment after a venous thromboembolism?

- provoked (e.g. recent surgery, trauma, significant immobility): 3 months

- unprovoked: 6 months

What is the 2-level Wells Score and what is it used for?

Two-level DVT Wells Score - used to calculate DVT risk

active cancer (treatment ongoing, within 6 months, or palliative):


Paralysis, paresis or recent plaster immobilisation of the lower extremeties:


Recently bedridden for 3 days or more or major surgery within 12 weeks requiring general or regional anaesthesia:


Localised tenderness along the distribution of the deep venous system:


Entire leg swollen:


Calf swelling at least 3 cm larger than asymptomatic side:


Pitting oedema confined to the symptomatic leg:


Collateral superficial veins (non-varicose):


Previously documented DVT:


An alternative diagnosis is at least as DVT:


DVT likely = 2 points or more

DVT unlikely = 1 point or less

What do you proceed to do if a DVT is likely on a 2-level Wells score?

- a proximal leg vein ultrasound scan should be carried out within 4 hours, and if the result is negative, a D-dimer test

- If a proximal leg vein ultrasound scan cannot be carried out within 4 hours, a D-Dimer test should be performed and low molecular weight heparin administered whilst waiting for the proximal leg vein USS (which should be performed within 24 hours)

What do you proceed to do if a DVT is unlikely on a 2-level Wells score?

- D-dimer test

- If it is postitive, a proximal leg vein USS within 4 hours

- If a proximal leg vein ultrasound scan cannot be carried out within 4 hours, low molecular weight heparin should be administered whilst waiting for the proximal leg vein USS (which should be performed within 24 hours)

What is the treatment for a DVT?

- LMWH or fondaparinux should be given initially after a DVT diagnosis

- a vitamin K antagonist (i.e. warfarin) should be given within 24 hours of the diagnosis

- the LMWH or fondaparinux should be continued for at least 5 days or until the international normalised ratio (INR) is 2.0 or above for at least 24 hours (whichever is longer)

i.e. LMWH or fondaparinux is given at the same time as warfarin until the INR is in the therapeutic range

- warfarin should be continued for at least 3 months.

- NICE advise to consider extending warfarin beyond 3 months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding

- this essentially means that if there was no obvious cause of provoking factor (Surgery, trauma, significant immobility) it may imply the patient has a tendency to thrombosis and should be given treatment longer than the norm of 3 months

- in practice most clinicians give 6 months of warfarin for patients with an unprovoked DVT/PE

- for patients with active cancer, LMWH is recommended for 6 months

What should you offer all patients with unprovoked DVT or PE who are not already known to have cancer?

Offer the following investigations for cancer:

- a physical examination (guided by the patient’s full history) and

- a chest x-ray and

- blood tests (full blood count, serum calcium and liver function tests) and urinalysis

Consider further investigations for cancer with an abdominopelvic CT scan (and a mammogram for women) in all patients aged over 40 years with a first unprovoked DVT or PE

When should you offer thrombophilia screening?

- not offered if patients will be on lifelong warfarin (i.e. won’t alter management)

- consider testing for antiphospholipid antibodies if unprovoked DVT or PE

- consider testing for hereditary thrombophilia in patients who have had unprovoked DVT or pE and who have a first-degree relative who has had DVT or PE

What are the contraindications to graduated compression stockings?

- known peripheral vascular disease

- leg or buttock pain on exercise

- previous or planned revascularisation surgery

- massive leg oedema where stockings are unable to be fitted

- leg conditions in which stockings would interfere e.g. dermatitis, recent skin graft, gangrene

What is the anticoagulation therapy used in VTE treatment?

Anticoagulation therapy

- prevent extension and recurrence (not thrombolytic)

standard approach

- immediate therapy with treatment-dose heparin (LMWH)

- overlap with warfarin until INR in therapeutic range (5 days minimum)

- then stop LMWH, continue warfarin for 3 months (monitor in anticoagulant clinic) and review duration

What does warfarin inhibit and what are the different types of warfarin?

Warfarin = Vitamin K antagonist

Inhibits factors II, VII, IX and X (and protein C and protein S)

- prevents formation and secretion of vitamin K dependent clotting factors by liver cells

- avoid in pregnancy - teratogenic and bleeding

- risk of major bleeding - 1-2% per year

When do you get hypersegmented neutrophils?

Whereas normal neutrophils only contain three or four nuclear lobes (the "segments"), hypersegmented neutrophils contain six or more lobes.

Hypersegmented neutrophils have classically been thought to be pathognomonic of the class of anemias called megaloblastic anemias (anemias caused by failure of bone marrow blood-forming cells to make DNA, often caused by vitamin B12 or folate deficiencies, or DNA-replication poisons).

However, in seeming contradiction to this, several studies have strongly associated neutrophil hypersegmentation with iron deficiency anemia

How do you treat Immune thrombocytopenic purpura?

If symptomatic and/or severe (platelets <20 x10^9/l) and prolonged then treatment is with steroids or splenectomy.

In an acute situation (e.g. pre-operatively) intravenous immunoglobulins or platelet transfusion may be given.

How may B12 deficiency present?

- thrombocytopaenia

- macrocytic anaemia

- lucopenia (With hypersegmented neutrophils due to abnormal nuclear synthesis)

What is ITP?

Defined as isolated low platelet count (thrombocytopenia) with normal bone marrow and the absence of other causes of thrombocytopenia. It causes a characteristic purpuric rash and an increased tendency to bleed. Two distinct clinical syndromes manifest as an acute condition in children and a chronic condition in adults.

ITP is an autoimmune condition with antibodies detectable against several platelet surface antigens.

What is the treatment of ITP

There is increasing use of Immunosuppresants such as mycophenolate mofetil and azathioprine because of their effectiveness. In chronic refractory cases, where immune pathogenesis has been confirmed, the off-label use of vincristine, a chemotherapy agent, may be attempted. However, this vinca alkaloid has significant side effects and its use in treating ITP must be approached with caution, especially in children.Intravenous immunoglobulin (IVIg) may be infused in some cases.

Splenectomy (removal of the spleen) may be considered, as platelets which have been bound by antibodies are taken up by macrophages in the spleen (which have Fc receptors). The procedure is potentially risky in ITP cases due to the increased possibility of significant bleeding during surgery.

What is TTP?

Thrombotic thrombocytopenic purpura is an idiopathic response to infection, trauma or heparin therapy and is part of a spectrum of disease that also includes haemolytic uraemic syndrome. There is also a micro-angiopathic anaemia.

Neurological symptoms are common. Patients may develop bleeding or thrombotic complications.

Treatment is supportive but steroids or plasmapheresis may be considered. Mortality is high.

How does ITP usually present in children?

ITP in children is usually acute, post-infection (e.g. post sore throat) and self-limiting.

Treatment is supportive but rarely required.

How does Von Willebrand disease present?

Von Willebrand’s disease is a congenital deficiency of von Willebrand factor (factor VIII related antigen).

This has 2 effects: reduced platelet adherence to connective tissue and minor reduction in factor VIII activity.

Symptoms are related to the platelet dysfunction (e.g. menorrhagia, epistaxis).

Treatment, if needed, is with recombinant factor VIIII.

(prothrombin time = normal, activated partial thromboplatin time (APTT) and bleeding time are prolonged.

What happens to kidney size in renal artery stenosis?

The stenosed renal artery may lead to a smaller, atrophied kidney

What are the main causes of renal artery stenosis ?

- atherosclerosis (in hypertensives and diabetics)

- fibromuscular hyperplasia (idiopathic in young or middle aged women)

How do you confirm/diagnose renal artery stenosis?

unequal sized kidneys (if unilateral)

- may be confirmed with renal arteriography

- or DTPA scanning before and after a captopril trial

What is the treatment of renal artery stenosis?

angioplasty and stenting (usually only successful in fibromuscular hyperlasia)

or bypass surgery.

ANGIOPLASTY: This is an endovascular technique that involves inflating a balloon within the narrowed artery to widen the vessel and improve flow. The balloon is introduced through a puncture site in either the groin (more common) or arm.STENT PLACEMENT: A stent is a metal device that is placed inside the artery that acts as a scaffold to hold the artery open. Stenting is usually performed in conjunction with angioplasty, through the same puncture site

ENDARTERECTOMY: This operation involves an abdominal incision and a 5-7 day hospital stay. During the procedure, the narrowed artery is opened and the plaque is removed. The opening in the artery is then closed and blood flow is restored to the kidney.BYPASS SURGERY: This method of repair also involves an abdominal incision and a 5-7 day hospital stay. A graft is placed to bypass or "go around" the area of blockage, thereby restoring blood flow and pressure to the affected kidney.

What is phaeochromocytoma associated with?

May arise de novo or associated with neurofibromatosis or MEN IIa (medullary thyroid cancer and hyperparathyroidism).

How does Graft v Host Disease present?

● Usually occurs at ~4 weeks after transfusion

● Fever (day 28), skin rash (day 30), diarrhea, abnormal liver function tests

● Death (day 51), usually due to sepsis because of leukopenia and pancytopenia

How do you diagnose Graft v Host Disease?

● Diagnosis based on clinical findings and laboratory and biopsy results

● Easily confused with severe viral illness or adverse reaction in severely ill patients if Ta-GVHD is not suspected - considered to be underdiagnosed and underreported

● Confirm diagnosis by finding donor lymphocytes or DNA in patient’s peripheral blood or tissue biopsy, with the appropriate clinical symptoms