Guideline No. ***
Queens’s Medical Centre, Paediatric Intensive Care Unit – Clinical Guidelines
Title: The Management of Abnormal Haemostasis on PICU
Version:
Date:
Review Date: ***
Authors: Dr. Damian Roland, Dr Kate Foreman, Dr Harish Vyas
Job Title: ***
Approval: ***
Distribution: ***
Clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt, contact a senior colleague. Caution is advised when using guidelines after a review date.
The emphasis of this guideline is acquired disorders of haemostasis. The diagnosis and treatment of inherited bleeding disorders will not discussed in detail; nor will therapeutic anticoagulation. The advice of a haematologist must be sought in these cases. The management of coagulopathy associated with cardiopulmonary by-pass is complicated and will not be discussed as this is not a situation encountered within the Nottingham Paediatric departments.
Please refer to the algorithm on page *. The following text will provide specific information about procedure, physiology, blood products and treatment but only as an addedenum to the algorithm. It is hoped therefore that ‘random’ clotting tests will hopefully be discouraged and avoided.
Tests
Paediatric clotting studies are sent in citrate tubes (pale blue tops), which should be stored in a fridge prior to sample collection. The following points are important:
1) 1.3 ml of blood collected from a free flowing is required. It is vital that no less (and no more) blood is collected to ensure the adequate ratio of products is obtained and avoid return of the sample.
2) Please remember that the blood and citrate should be mixed in the tube by inverting the tube several times as soon as the sample is taken. If the sample of blood is obtained from a heparinised line then at least 5-10 ml of discard should be taken prior to collecting sample.
D-dimers and Fibrinogen must be specifically requested if required. They are not part of a routine clotting screen.
· Prothrombin Time
The prothrombin time (PT) is used to assess the extrinsic pathway of clotting, which consists of tissue factor and factor VII, and coagulation factors in the common pathway (factors II [prothrombin], V, X, and fibrinogen).
· Activated Partial Thromboplastin Time
The activated partial thromboplastin time (APTT) is used to assess the integrity of the intrinsic coagulation pathway (prekallikrein, high molecular weight kininogen, factors XII,
XI, IX, VIII) and final common pathway (factors II, V, X, and fibrinogen), and to monitor heparin therapy.
· Thrombin Time
The thrombin time (TCT) measures the final step of the clotting pathway, the conversion of fibrinogen to fibrin.
Evaluating the presence of heparin in the sample - When evaluating an isolated prolonged APTT or TT, if heparin contamination is possible it is necessary to exclude this as the etiology. Ask the lab to perform the following on the original blood sample (In practice this is likely to have already occurred). It may be necessary to redraw a blood sample using a definitely uncontaminated peripheral vein.
1. If a prolonged TT corrects after the addition of protamine, heparin or a heparin-like material is present.
2. Perform a thrombin time (TT) and reptilase time (RT). Heparin is present if the TT is prolonged and the RT is normal.
· Fibrinogen
Fibrinogen's functional activity is measured when used as part of a coagulation screen. The plasma fibrinogen concentration is usually low in acute decompensated DIC, but may be elevated as an acute phase reactant in inflammatory conditions including sepsis and malignancy.
· D-dimers
Fibrin D-dimers are degradation products of cross-linked fibrin. Elevated levels are the most common abnormality in disemminated intravascular coagulation (DIC). A single test only is required. The exception being meningococcal septicaemia but the advice of the PICU consultant on call or haematologist should be sought before requesting this.
Blood Products
· Fresh Frozen Plasma
FFP contains high levels of all coagulation proteins. It should be transfused as soon as possible but must be within 4 hours of being thawed from frozen. Transfused FFP should be ABO compatible. Adverse effects include allergic reactions, infections, haemolysis, transfusion related acute lung injury and fluid overload.
All FFP for children born after 1st January 1996 is methylene blue treated FFP (to reduce the risk of transfusion transmissible viruses).
· Cryoprecipitate
Cryoprecipitate contains high levels of fibrinogen together with factors VIII and von Willebrand's factor. Transfusion may be indicated in the treatment of DIC and massive transfusion.
· Platelets
Platelet transfusion is used to treat and prevent bleeding in patients with low platelet counts or defects of platelet function. In the UK, platelet concentrates are produced from whole blood using the buffy coat method of preparation, or by platelet pheresis according to agreed National Blood service guidelines
Platelet concentrates obtained by either method contain approximately the same number of platelets, and comparative studies have shown them to be therapeutically equivalent in terms of post-transfusion platelet increments, haemostatic effectiveness with a similar incidence of side effects. In addition, platelet transfusion contains coagulation factors VII and IX, which are often the depleted factors following massive transfusion, and so platelets are also indicated in the treatment of bleeding associated with haemodilution.
The management of functional platelet disorders should be discussed with a Haematologist.
Detailed discussion of the use of platelet transfusion in oncology patients is outside the scope of this guideline. Further information may be found in {oncology guideline} or discuss with Oncologist/Haematologist.
Transfusion is not without risks including allergic reaction, infection, alloimmunisation and transfusion related acute lung injury .
· The following recommendations for Platelet transfusion are made. The principle indication being bleeding in a thrombocytopenic patient:
In a bleeding patient aim for platelet count greater than 50x109 except in patients with multiple trauma or CNS injury when platelets should be maintained above 100x109.
Serious spontaneous bleeding due to thrombocytopenia alone is unlikely to occur at platelet counts greater than 10x109. In the absence of sepsis, concurrent antibiotic use, other abnormalities of clotting or other risk factors for bleeding, transfuse once platelets have fallen to below 10x109. In the pyrexial/septic patient in may be advisable to keep platelets >20x109 but this is at the discretion of the treating physician.
Do not assume the platelet count has risen to desired levels. It may be prudent to check prior to procedure.
Procedure / Aim for Platelets > /109Bone Marrow Biopsy/Aspiration / Any level (must ensure adequate pressure applied following procedure)
Lumbar Puncture / >30
Spinal procedures, Oesophageogastroduodenoscopy and biopsy
Insertion of surgical central venous line, Laparotomy
Lung biopsy / >50
Liver Biopsy
Brain or eye operations / >100
Transfusion volume:
Patient less than 15kg 10-20mls/kg
Patient over 15kg single unit (approx 250mls)
If small volumes are being transfused i.e 100mls and less and a single unit bag has been supplied it is important to give the most concentrated solution possible. Therefore the bag should be hung under gravity for 30mins before the appropriate amount is drawn off.
· Plasma and Platelet Compatibility
Donor platelets and recipient should be ABO and RhD matched. If this cannot be ensured, then compatible components lacking high titre anti-A or -B should be transfused to Group A or B recipients. For platelet and plasma transfusions, plasma compatibility should be ensured whenever possible. Both products contain sufficient red cell material to stimulate Rhesus immunisation. In the unlikely event rhesus positive platelets are given to a resus negative female, anti D must be given (please ring blood bank with regards to dosage required)
· Vitamin K
The vitamin K dependent factors are II, VII, IX and X. Deficiency of these factors leads to a prolongation of PT. Ill children on antibiotics often develop an acquired type deficiency.
In the absence of bleeding, if PT ratio is greater than 1.5 and there has been reduced vitamin K intake and continued reduction in intake is anticipated (eg. no enteral or total parenteral feeding), then consider intravenous vitamin K (given slowly). Response is rapid within 30-120 minutes, but repeat doses may be required.
Age / Dose / Age / Dose< 1 year / 1mg / 5-10 years / 5mg
1-5 years / 2.5mg / >50kg / 10mg
If the patient is bleeding, and prolonged PT is the only abnormality then FFP is first line treatment and vitamin K may be considered if deficiency is suspected.
Haemorrhagic disease of the newborn is managed with vitamin K. Management is discussed in {neonatal guideline}.
Disseminated Intravascular Coagulation
· Definition
Systemic activation of coagulation from various disorders leading to widespread consumption of coagulant factors more often predisposing to bleeding but occasionally resulting in microvascular thrombosis and organ dysfunction.
· Clinical features
Manifestations of acute DIC in addition to the most common sequelae of bleeding include thromboembolism and dysfunction of the kidney, liver, lungs, and central nervous system. Petechiae and ecchymoses are common in conjunction with blood oozing from wound sites, intravenous lines, catheters, and, in some cases, mucosal surfaces. The thromobotic component is rare but most often seen in meningococcal septicaemia.
· Diagnosis
The laboratory findings that are used to confirm the diagnosis of DIC are somewhat different in acute and chronic disease.
Acute DIC - The diagnosis of acute DIC is suggested by the history (sepsis, trauma, malignancy), clinical presentation, moderate to severe thrombocytopenia (less than 100x109) and the presence of microangiopathic changes on the peripheral blood smear. Serial tests and trends in laboratory results suggesting ongoing consumption of clotting factors are more helpful in diagnosis than any single test.
Study / Change / RememberD-Dimers / Any level above normal significant / DIC unlikely without elevation
May rise following surgery or trauma
Fibrinogen / Decreases / Acute phase reactant so levels may be normal or increased
Thrombocytopenia / <100 or downward trend / Sensitive but not specific sign
PT/APTT / Raised / A later onset sign so a normal value does not preclude diagnosis
· Differential
Be cautious of diagnosing DIC in the precence of liver disease. Patients with TTP-HUS present with thrombocytopenia and a microangiopathic blood smear but usually have normal levels of the coagulation components.
· Treatment
Although mortality associated with DIC is high (40-80%), major bleeding occurs in only a minority of patients, and death is often as a result of underlying disease.
Treatment is of the underlying cause with blood component therapy being supportive. Treatment is most relevant in active bleeding or when an intervention that increases bleeding is predicted.
The most important assement of haemostasis is clinical and a platelet count alone may be the best indicator of response to treatment. Coagulation screens need be performed no more than once a day unless blood products are prescribed in which bloods should be sampled 4 hours after infusion to assess response to therapy.
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