Something in the blood?

By: Navdeep Brar, Andrew Shute, John Ong Student Grand Round Tuesday, 25 Nov 2003

PC

 11.11.2003

 Pleasant 78 yr old lady presenting in A&E with acute right thoracic pain radiating from back to anterior chest

The Patient History

HPC

      Receiving treatment for recent pleural effusion (18.09.2003) Dry, non-productive cough for 7/52; some SOB; ° haemoptysis; ° wheeze Pain started early previous morning Pain – sharp, sudden, constant; associated headache; ° N & V Not relieved by paracetamol or posture; worse on deep inspiration ° recent travel, immobility or leg pain

PMH

       Recurrent admissions for similar complaints over last 4 years 2 x previous PE (1992, 1999) Subdural haematoma (1992) 2 x TIAs (1994 & 2000) Hiatus hernia; acute pancreatitis; diverticulitis Scoliosis with back pain ° JTHREADS; ° MI

PMH continued

 Warfarinised after first PE in March 1992  April 1992 presented with daily, constant headaches for 5/52; worse in mornings, when coughing and straining  CT showed bilateral subdural haematoma L > R; INR 2.7

 Warfarin stopped.

 Started on aspirin 75mg od

PMH continued

 June 1992: CT check up showed persistent R hemisphere, chronic subdural haematoma with mass effect and shift.

 R frontal burrhole drainage at Atkinson Morley Hospital  Sept 1992 check up showed good progress

PSH

 Cholecystectomy (2001)  Bilateral cataract removal (1990s)  Neurosurgical evacuation of sub-dural haematoma (1992)  Hysterectomy (1990)

MH

 Omeprazole 40mg od  Aspirin 300mg od  Amoxycillin 500mg tds  Occasional paracetamol; ° herbal, complementary or recreational drugs  NKDA or side effects

GH

     “Not as good as it used to be” though “previously quite healthy” Lost some weight and mild anorexia since cough started Sleeps well No exercise but leads an active and busy life Her back ache can stop her doing some activities

SH

       Widowed for 18 years; 4 sons: 51, 46, 39 (non-identical twins) Lives in 3 bedroom, terraced house with her youngest son Has good family and home support Enjoys reading and is active around the house Retired though used to work as a typist, temp. and school help ° smoking occasional alcohol

FH

 Father – glaucoma  Brother – died aged 56 from an embolism?

 Brother – suffered from depression and died from an overdose?

 CVS  Resp.

 GI   GU Neuro.

 MSS

Systems

- right thoracic chest pain - ° palpitations, ° paroxysmal nocturnal dyspnoea, ° ankle swelling - ° SOBOE - sleeps with 2 pillows - often has constipation or diarrhoea - occasional heartburn - mild nocturia - occasional migraine - numbness on her right hand (medial distribution) - prescription glasses, ° hearing problems - ° stiffness or pain in limbs - constant backache

O/E 11.11.2003

       Px c/o chest pain and headache; seems quite tired and ill Pulse: 97, BP: 152/85, RR: 22, Temp: 37 o , O 2 sats: 96 air, JVP 5 mm, HS I + II + 0 o oedema, calf swelling or tenderness Chest resonant AE ↓ right base, right basal dullness o masses or organomegaly

Investigations

  FBC, D-dimers, Blood culture, U&Es, LFT, Bone Profile, glucose, CK, CRP, Trop T, ABG ECG and CXR         Albumin 32 (35-48) Sensitive CRP 99.1 (0-8) Hb ↓ 11.3 (11.5-16) ABG: PaO2 ↓ 8.62 (>10.6) Gamma GT 43 (0-30) D dimers ↑ 0.79 ECG – sinus rhythm, RBBB, Qs III, CXR – small right pleural effusion

Differential diagnosis

   PE Pleural effusion exacerbation Other chest infection Plan:     Troponin T, thrombophilia screen, V/Q scan, ?CTPA

Co-dydramol 2 tabs oral Voltrol Fragmin 50 mg 10000 SC

Pulmonary Embolism

 Most often due to venous thrombus in the abdomen, pelvis or legs  Part of a clot breaks off and passes through the heart before lodging in the pulmonary circulation  Ventilation is normal but perfusion is reduced

PE Risk Factors

 Any cause of recent immobility or hypercoagulabiltiy:  recent surgery; stroke; MI  prolonged bed rest (E.g. infection)  Thrombophilia  Disseminated malignancy  Pregnancy, postpartum; The Pill/HRT  Advanced age

PE - clinical features

 Depend on number, size and distribution of emboli:  Small - often asymptomatic  Large - often fatal  Acute breathlessness; pleuritic chest pain; haemoptysis; dizziness.

 Pyrexia; cyanosis; tachypnoea; tachycardia; hypotension; raised JVP; pleural rub/effusion

Why PE?

 Previous history  Advanced age  Immobility for last 7 weeks with cough  SOB; Pleuritic chest pain; raised JVP  Evidence of pleural effusion  Support from ECG and CXR  PaO2 ↓ 8.62; D dimers ↑ 0.79

Chest X-ray

VQ Perfusion Scan

12.11.2003

 ° SOB, ° headache, pain ↓, “feels well”  V/Q scan – unmatched perfusion defect in the right midzone anteriorly, but unchanged since previous scan on 09.01.2002.

 This indicated that there was no evidence of a new PE

13.11.2003

  ABG - PaO2 11.71 kPa, PaCO2 4.83 kPa Px feels much better 14.11.2003

   Px discharged – probable muscular pain as result of cough combined with underlying pleural effusion Aspirin 300mg od, Ibuprofen 400mg prn, Paracetamol 1g prn Results of thrombophilia screen to be sent to GP if abnormal

Warfarin

Warfarin Sodium

 Anti-coagulant acts by inhibiting vitamin K dependent coagulation factors > Factors II, VII, IX, X & anti-coagulation proteins C & S  Racemic mixture of R + S enatiomers > S enatiomer has 2-5 times more anti-coagulant activity  Takes at least 48-72hrs for anti-coagulation effects to develop fully > Immediate effect Heparin must be given concomitantly

Pharmacokinetics

 Absorption > completely absorbed after oral administration-peak concentration attained 1st 4hrs.

 Distribution > No difference after I.V and oral administration > 0.14L/kg volume of distribution > Concentration in foetal plasma approach maternal values > 99% bound to plasma proteins

Pharmacokinetics

 Metabolism > Eliminated almost entirely by metabolism-hepatic microsomal enzyme (cP450) & reductases.

 Excretion > Excreted in urine & bile > Effective t 1/2 = 20-60 hours  Elderly > > No significant age-related difference in phamacokinetics of racemic warfarin As age increases less warfarin is required to produce therapeutic levels of anti-coagulation

Phamacokinetics

 Renal dysfunction > No dosage adjustment necessary for patients with renal failure  Hepatic dysfunction > can potentiate the response to warfarin- through impaired synthesis of clotting factors and decreased metabolism

Indications

 Prophylaxis and/or treatment: > Deep venous thrombosis > Pulmonary Embolism > Atrial Fibrillation with risk of embolisation  > Cardiac valve replacement to prevent emboli developing on these Post Myocardial Infarction- reduce risk of death, recurrent MI, stroke & systemic embolisation.

Dosage & Administration

 Individualised for each patient according to the particular patients prothrombin time, reported as international normalised ratio- INR.

 INR is a value derived from a standardised laboratory test that measures the effect of an anticoagulant.

 Normal blood has an INR 1.

 Therapeuitc anti-coagulation aims to achieve an INR of between 2.0-3.5.

Dosage & Administration

    DVT & PE > INR 2.0-3.0 is sufficient for prophylaxis and treatment AF > Effects of warfarin in reducing thromboembolic events such as stroke were similar at high INR 2.0-4.5 or low INR 1.4-3.0. Post M.I

> Wafarin therapy should be initiated early (2-4 weeks post M.I) and adjust dosage to maintain INR of 2.5-3.5 long-term.

Cardiac valve replacement > > Mechanical heart valves long term prophylaxis to an INR of 2.5-3.5.

Bioprothetic heart valves for warfarin therapy to an INR 2.0-3.0 for 12 weeks after insertion.

Dosage

 Initial Dosage > > > Varies for each Individual according to patient’s drug sensitivity Large loading dose may increase risk haemorrhages & no evidence for increased protection against thrombi formation Low doses recommended for elderly and/or debilitated patients  Maitenance > > 2-10 mg daily continued until the danger of thrombosis and embolism pass

Side Effects

 Fatal or non-fatal haemorrhage from any tissue or organ > may present as paralysis, headache or pain in other areas, dizziness, shortness of breath, weakness, hypotension and unexplained shock.

 Bleeding-occurs when PT/INR is within therapeutic range > may unmask a previously unsuspected lesion e.g tumour or ulcer.

 Infrequent adverse reactions > These include Hypersensitivity reactions, systemic cholesterol microembolization, purple toes syndrome, vasculitis, hepatitis, cholestatic hepatic injury, jaundice,elevated liver enzymes.

Warnings

  Narrow therapeutic index drug and maybe affected by factors such as other drugs and dietary vitamin K.

Administration of drugs in the following conditions need to considered in terms of risks of therapy weighed against benefits:  Lactation       Severe to moderate hepatic insufficiency Infectious Diseases Trauma Surgery Known or suspected Deficiency in Protein C mediated Anticoagulant Response Polycythemia vera, vasculitis, severe diabetes

Subdural Haematoma

Definition

 SDH is defined as “an accumulation of blood in the space between the dura and the dura mater following the rupture of a vein(s) running from the hemisphere to the sagittal sinus.”

Epidemiology

 1/3 of all severe blunt head trauma (GSC < 9) in US (UK?)  Occurs in men > women

Dura reflected back to show bridging veins that drain from the cortex to sagital sinus.

Dura reflected back to show a subdural haematoma.

Pathology

 Rupture of veins within the dura  leakage + accumulation of blood in subdural space  Commonly due to blunt head trauma and very rarely occurs spontaneously  Generally divided into 3 groups: Acute, Subacute, and Chornic

Pathology (Cont’d)

 Acute - rapidly clotting blood collection 0-2 days of injury. Associated with high mortality (20%) and morbidity rates.

 Subacute – clotting blood collection within 3-7 days of injury  Chronic – 2-3 weeks after injury  Note: Complicated SDHs are associated with 50% mortality rates. ( Rupture is assumned to occur at time of acute injury)

Signs

 Raised ICP  Localized neurological symptoms  Shifted midline structures away from side of the clot (if clot is sizeable)  Tentorial herniation and Coning (may occur if untreated).

Symptoms

 headache, drowsiness, confusion  Physical + Intellectual slowing,  sleepiness,  personality change  unsteadiness  symptoms fluctuate in about 35% of patients and may surface a few weeks to a few months after the injury

Risks Factors / People At Risk

 Infants  adhesions in subdural space absent at birth and develop with age  bilateral SDHs are more common in infants  Victims of child abuse  Associated with Inter-hemispheric SDH  Alcoholics  Prone to head trauma, thrombocytopenia, prolonged bleeding times

People At Risk (Cont’d)

 Elderly  (accident prone, atrophic brains make connecting more susceptible to rupture)  Epileptics  Patients on Anti-coagulants  Haemophiliacs veins

Investigations

 FBC  Coagulation Profile (INR, PT, aPTT)  Electrolytes  Type and screen/cross  CT  MRI (if CT is insufficient)

Diagnosis



Acute SDH

 typically a hyperdense

(white) crescentic mass

 along the inner table of the skull, most commonly over the cerebral convexity in the

parietal region.

Diagnosis (Cont’d)



Subacute Phase SDH

 lesion becomes isodense (wrt brain) and is harder to see on a CT scan  MRI and contrast CT scan should be used Non-contrast CT scan MRI

Diagnosis (Cont’d)



Chronic Phase SDH

 Lesion becomes hypodense and is easy to diagnose on normal CT scans Commonly bilateral, and have areas of acute bleeding, which result in heterogeneous densities

Differential Diagnosis

        Stroke, Cerebral tumour, Dementia, Subdural empyema, Meningitis, Subarachnoid haemorrhage, Epidural haematoma, Elderly and child abuse

Initial Management

    Use GCS to ascertain level of consciouness (though it may fluctuate) Consider Intubation if GCS < 12 or other conditions present that threaten airway/breathing.

Check for signs of focal neurological deficits & ICP Recommended that any head trauma that results in a GCS <15 in a patient without the influence of any mind-altering or intoxicating substances, should require an urgent CT scan

Management (Cont’d)

 Some degree of midline shift should be present with moderate or large SDHs.    If midline shift absent  . suspect contralateral mass If midline shift excessive  , suspect brain oedema. If SDHs in posterior fossa  cerebellar injury.

suspect Parenchymal  Interhemispheric SDH - falx cerebri appears thickened and irregular, often associated with child abuse.

Management (Cont’d)

 Rx depends on  (1) clinical signs and symptoms,   (2) size of the clot, and (3) area of the brain involved.  Asymptomatic and minor SDHs (i.e. having no altered state of consciousness) can be watched over time  Surgery is needed for SDH when there are    Signs of brain compression (confusion, altered level of consciousness), Midline displacement >5.0 mm, increased intracranial or posterior fossa pressure

Management (Cont’d)

 Surgical intervention normally involves craniotomy and evacuation i.e. Identify and control bleeding sites, making a large cranial flap, opening the dura and remove the clot with suction, cup forceps, and/or irrigation.  If in a medical emergency (life threatening), Burr hole surgery is done to relieve pressure though it is not curative. When patient is stable, craniotomy and evacuation is done.

Complications

Postoperative complications      Elevated ICP Brain Oedema New or recurrent bleeding/haematoma Infection Seizures Chronic SDH    Recurrent hematoma (50%) Infection (eg, subdural empyema, wound) Seizures (up to 10%)

Prognosis

 Definitive prognosis often is not possible at the time of emergency department evaluation.

 Ultimate prognosis is related to the amount of associated direct brain damage and the damage resulting from the mass effect of the SDH.