4um.com

News Movies Music Medicine Computers Ireland Cool Sites Search

Click Here to return to the
 Tutorial Index Page

---

Coagulation Disorders and Anaesthesia

---

All tutorials located on this site are the property of Patrick Neligan and are for personal study purposes only. They are not peer reviewed and no responsibility is taken for inaccuracies. These tutorials must not be reproduced without permission or used in any other publication.

COAGULATION DISORDERS AND ANAESTHESIA

• Impaired Function Of Blood Vessels
• Impaired Function Of Platelets
• Impaired Function of Coagulation Pathways

HAEMOSTATIC FAILURE 

Impaired Function of:

• Blood Vessels
• Platelets
• Coagulation Pathways

IMPAIRED FUNCTION OF BLOOD VESSELS 

1. CONGENITAL

• Ehler’s Danlos syndrome
• Osteogenesis Imperfecta
• Pseudoxanthoma Elasticum
• Marfan’s Syndrome
• Hereditary haemorrhagic telangiectasia

1. ACQUIRED

• Vitamin C deficiency (Scurvy)
• Steroids
• Vasculitis
• Amyloidosis

Top of Page

IMPAIRED FUNCTION OF PLATELETS

CONGENITAL

• Wiscott-Aldrich syndrome

ACQUIRED

DECREASED PRODUCTION

• Leukaemia
• Cytotoxic drugs
• Marrow infiltration
• Aplastic anaemia

INCREASED DESTRUCTION (Platelets)

1. IMMUNE:

• Autoimmune – Idiopathic Thrombocytopaenia Purpura
• Isoimmune

2. NON IMMUNE:

• Splenomegaly
• Disseminated Intravascular Coagulopathy
• Thrombotic thrombocytopenia purpura

DISORDERED FUNCTION

• Drugs: e.g. Aspirin
• Uraemia
• Liver disease
• Myeloproliferative disorders
• Von Willebrand’s disease

Top of Page

IMPAIRED FUNCTION OF COAGULATION PATHWAYS

CONGENITAL

• Haemophilia A & B

ACQUIRED

• Liver disease
• Dysproteinaemias
• D.I.C.
• Heparin and Warfarin

Top of Page

COMMONLY ENCOUNTERED
COAGULATION DISORDERS

VON WILLEBRAND'S DISEASE

• The commonest hereditary haemostatic disorder
• Autosomal Dominant, Marked phenotypic variation
• Qualitative or quantitative deficit of vWF
• vWF is the bridging molecule between the primary phase of haaemostasis and coagulation. Enables platelets to loccalize and adhere to sites of injury, facilitates recruitment and aggregation of other platelets
• Combines with factor VIII to form the full coagulation molecule (acts as a carrier protein)
• Three types: Types 1 and 2 are quantitative defects, Type 3 is qualitative – mutant protein
• Spectrum of severity, depending on vWF levels:

Frequent nose bleeds »heavy periods »mucosal bleeds »haemarthoses.

• Severe disease: decreased vWF and Factor vIII

Epidemiology

Incidence: 1%, mostly undetected. M=F

Diagnosis

• Prolonged Bleeding time and APTT; normal PT, normal Platelet count.
• Antigen assays of vWF and Factor VIII performed if suspected (radioimmunoassay).
• VWF activity is assessed using a ristocetin cofactor assay.

Bottom line:

Normal Bleeding time and APTT does not exclude the diagnosis of Von Willebrand’s disease

Treatment

DDAVP: Mild to moderately severe disease.

• Induces the release of vWF from endothelial storage granules.
• 2-3 x increase in vWF levels in 30-60 mins, Lasts 6 hours.
• Given 2-3 times a day. Tachyphylaxis may occur.
• DDAVP: good for minor bleeding, minor surgery (dental extractions).

Major surgery:

• Cryoprecipitate or FFP or intermediate purity forms of factor VIII concentrate
• Preop: 4 bags cryo/10kg body weight -will increase levels above 25% for 18h (normal BT x 6-12h)
• Post op: 2 bags cryo 10/kg @ 12 hourly intervals x 4
• Then 2 bags daily x 6 days

Top of Page

IDIOPATHIC THROMBOCYTOPENIA PURPURA (ITP)

• Post viral syndrome: Autoimmune, antiplatelet antibodies
• IgG antibodies against platelet membrane glycoproteins IIb/IIIa.
• Platelet-antibodies phagocytosed by RES (mostly in the spleen) – shortened platelet life span. Platelet transfusion ineffective.
• Most acute cases self limited, occurring mostly in children Some hospitalised, requiring steroids.
• 10% Develop a chronic disorder (young women) with splenic sequestration of platelets: may require splenectomy.

Clinical Features

• Petechial Haemorrhage
• Easy bruising
• Skin Purpura
• Menorrhagia
• Mucosal haemorrhage
• Rarely, intracranial haemorrhage

Diagnosis 

Reduced Platelet count (10 – 50 x 10⁹ l^-1)

• Increased megakaryocytes in an otherwise normal marrow.
• No splenomegaly.

Treatment

1. Steroid therapy, in high dose
2. Splenectomy (75 – 80% remission
3. Cytotoxic agents

Anaesthetic Management 

1. Costicosteroid supplementation
2. Intravenous gamma globulin 1g/kg/day for 2 days pre op
3. Regional techniques by and large avoided
4. Laryngoscopy and intubaation performed with great care
5. to avoid mucosal bleeding.
6. Avoid intramuscular injections.
7. Central lines are avoided.

For splenectomy:

1. Pneumococcal vaccination pre op.
2. Platelets should be available for transfusion, but not until the Splenic pedicle has been ligated.
3. Platelet count carefully monitored post op.

Top of Page

HAEMOPHILIA

Haemophilia A = factor VIII deficiency

Haemophilia B = factor IX deficiency

Haemophilia A

• X – Linked recessive
• Deficiency of factor VIII
• 1/10,000 males worldwide
• Factor VIII is genetically mapped on Chromosome 10, and produced in the liver, spleen, kidney and lymphoid tissue
• Symptoms correlate with functional factor VIII activity:

1ml of normal plasma contains 1 unit or 100% factor VIII activity.

Diagnosis

• Family history of bleeding disorder
• Preliminary blood tests: APTT, PT, Thrombin time, Bleeding time
• In haemophilia A and B the APTT is prolonged and the PT and the bleeding time are normal
• If the bleeding time is prolonged, suspect Von Willebrands disease
• Specific factor assays to differentiate A from B

Treatment

Factor VII replacement is the cornerstone of therapy

Two forms of factor VII:

1. Derived from concentration human serum.
2. Recombinant factor VII - synthesized from hampster cells in culture

In emergencies, Fresh frozen plasma or cryoprecipatate may be used.

Complications of treatment:

1. Viral infections
2. Factor VIII inhibitors

Anaesthetic Management

1. Factor VIII concentrate 1 hour before procedure, the level is maintained at 50% for 4 postoperative days.
2. Nasotracheal intubation is contraindicated, care with intubation and laryngoscopy to avoid trauma.
3. Regional techniques and central lines avoided.
4. PCA or morphine infusions post op.
5. Factor VIII levels carefully monitored post op.
6. Aminocaproic acid may be given as an adjunct in e.g. dental surgery to prevent clot lysis post op.
7. DDAVP can be used, but only in moderate disease with minor bleeding.

Top of Page

HAEMOLYTIC URAEMIC SYNDROME

A group of diseases occurring in children with a classic triad:

1. Microangiopathic haemolytic anaemia
2. Thrombocytopenia
3. Renal Failure

• An epidemic disease that presents after a prodromal diarrhoeal illness; as the child is recovering.
• Occurs in children 1 – 3 years of age
• Cause: Verotoxin producing E. Coli serotype 0157:H7
• Absorbed Verotoxin damages endothelium, leading to platelet and microvascular pathology
• Third world variant of HUS involves infection with Shigella, and has a poorer prognosis.

Clinical Features

Presentation follows 5 - 10 days following a prodromal illness

Prodrome:

Gastrointestinal in nature: pain, diarrhoea, vomiting, fever

Presentation:

• Haemoglobin 4 – 6 g/L,
• Platelet count 20 – 50,000
• Blood Film: microangiopathic changes
• W.C.C > 10,000
• Coomb’s test negative
• 50% anuric, 25% oliguric, Haematuria / moderate proteinuria

Management

• Treatment is supportive:
• Renal failure is managed with fluid restriction and dialysis (70%)
• Anaemia, if symptomatic treated with transfusion
• Hypertension and convulsions are treated appropriately
• In most cases haemolysis and thrombocytopenia are resolved in 8 – 10 days, 75% are resolved in 21 days, oliguria usually lasts 12 days.
• Most patients do not require ICU admission
• Other treatments available:
• Anticoagulants, streptokinase, aspirin, plasmapheresis

Top of Page

DISSEMINATED INTRAVASCULAR COAGULOPATHY 

• D.I.C. is a syndrome covering a broad spectrum of coagulation disorders, ranging from localised occlusive thrombus to explosive activation of all circulating coagulation factors with deposition of fibrin throughout the microcirculation.
• The depletion of these factors (consumption exceeds the ability to replace) leads to a bleeding disorder (defibrinogenation), with simultaneous depleton of naturally occurring inhibitors of fibrinolysis ( Protein C, Antithrombin III) which exacerbates the coagulopathy.

Pathogenesis of D.I.C.

1.ENTRY OF TISSUE THROMBOPLASTINS, CONTAINING A HIGH PHOSPHOLIPID CONCENTRATION, INTO THE BLOODSTREAM

• Stimulation of the coagulation cascade

Occurs in:

• Extensive tissue damage: trauma / surgery
• Disseminated malignancy
• Acute intravascular haemolysis (ABO)

2.ENDOTHELIAL INJURY

Severe damage to the vessel wall endothelium

• Platelet activation
• Activation of coagulation cascade by the intrinsic pathway

Occurs in:

• Gram negative septicaemia
• Burns
• Hypoxia / hypotension /acidosis

DIRECT PLATELET ACTIVATION

• Sepsis
• Viraemia
• Antigen-antibody complexes

Top of Page

Clinical Manifestations 

D.I.C is an important marker for the presence of severe systemic illness

VARIANTS:

1. Mild abnormalities in laboratory coagulation studies

2. HAEMORRHAGE:

• 90% of clinical D.I.C.s. Varies from purpura to severe ecchymosis, GIT haemorrhage, persistant ooze from venipuncture sites.

3. CLINICAL THROMBUS

• Apparent in 25% of total, but the presenting feature in only a few.
• Major arterial / venous thromboembolism is uncommon

4. ORGAN DYSFUNCTION

• Multioragan dysfunction syndrome

Mild D.I.C:

• Prolonged PT / APTT / TT
• Decreased platelets
• Increased F.D.Ps – measured as D-dimer

SEVERE D.I.C:

Reduced fibrinogen

Fragmented red blood cells

Diagnostic:

Platelets <100 x 10⁹

Fibrinogen < 1.0 g/L

Top of Page

Conditions associated with D.I.C.

1. MALIGNANCY

• Mucin secreting adenocarcinoma
• Prostatic carcinoma
• Acute promyelocytic leukaemia

2. INFECTION / SEPSIS

• Gram negative organisms
• Meningococcal septicaemia
• Staph aureus
• Viral disease

3. OBSTETRICS

• Abruptio placentae
• Amniotic fluid embolus
• Retained placenta
• Eclampsia

4. LIVER DISEASE

• Cirrhosis
• Fulminant hepatic failure

5. TRAUMA AND SURGERY

6. IMMUNE RESPONSE

• A.B.O. Incompatibility
• Anaphylaxis

7.MISCELLANEOUS

• Hypoxia
• Heat exhaustion
• Snake venoms

Top of Page

Top of Page
4um.com