Blood Disorders Flashcards
Thrombocytopaenia
Low platelets
Can be due to reduced platelet production, increased platelet destruction or sequestration of platelets (splenic pooling)
Aggregometry
Diagnostic test of choice for platelet function defects
Involves using a spectrophotometer to test light impedence of platelets in plasma. If the absorbance value is low, i.e., no light impedance, platelets have clotted. If the absorbance value is high, i.e., light impedance, platelets have not clotted. Agents are added in order to test clotting, e.g., collagen, thrombin, adrenaline.
APTT
Activated partial thromboplastin time
Activator added to platelet-poor plasma in the presence of Ca+2 and phopholipids to trigger XII —> XIIa
Normal: 24-37 seconds
Measures all factors except factor VII, most sensitive to XII and XI
Commonly prolonged in haemophilia (reduced VIII and IX)
What does a prolonged APTT indicate?
That there is a deficiency of a factor in the intrinsic or common pathway or that there is an inhibitor present. Next step is to attempt to correct the APTT
Isolated VII deficiency test results
Normal APTT but very prolonged prothrombin time
If APTT does not correct, what is indicated?
That there is an inhibitor present rather than a factor deficiency
Clotting inhibitors
Lupus anticoagulant
Acquired factor inhibitors
Unfractioned heparin
Dabigatran (oral thrombin inhibitor)
Prothrombin ratio
Prothrombin time of patient/Prothrombin time of normal pooled control
Normal = 0.8-1.2
Add TF to platelet-poor plasma in the presence of calcium and measure clotting time (around 12-15 seconds)
Used to monitor warfarin therapy
What does the prothrombin ratio detect?
Defects in II, VII and X (three of the four vitamin K dependent factors)
INR
International normalised ratio
Corrected PR used for warfarin monitoring. Necessary because clotting time and therefore PR can be variable depending on source of thromboplastin.
Thrombin clotting time
Add thrombin to platelet-poor plasma and measure clotting time (dependent on thrombin concentration used)
Sensitive to heparin, dabigatran, fibrin degradation products and fibrinogen abnormalities
Lupus anticoagulant
Antibodies in plasma that bind phospholipid
Prolongs APTT and 1+1 but doesn’t interfere with physiological clotting
These people don’t bleed
Antiphospholipid syndrome
Antibody binds endothelium causing excess clotting
Haemophilia A
X-linked condition
Factor VIII
Treated by factor VIII replacement, given prophylactically in children to prevent joint damage
Haemophilia B
X-linked condition
Factor IX
Treated by factor IX replacement, given prophylactically in children to prevent joint damage
Von Willebrand’s disease
Autosomal dominant (type 1 + 2) or recessive (type 3)
Defect of primary haemostasis resulting from reduced VWF
Patients won’t get proper platelet plugs
Because factor VIII circulates bound to VWF, VIII may also be reduced and give coagulation effects
Why do some antibiotics interact with warfarin?
Some antibiotics disrupt the microbiota of the gastrointestinal tract which can reduce fat and soluble vitamin absorption, therefore vitamin K absorption is reduced and patients can become deficient. Since vitamin K is a wafarin antagonist, the effects of warfarin in these patients can be exacerbated and should be monitored.
Fibrinolysis
Breakdown of fibrin
Labs can measure the level of D-dimer in the blood, which are cross-linked fragments of fibrin and imply clot degradation
High levels of D-dimer found in venous thrombosis and DIC (sensitive but not specific)
Virchow’s triad
Stasis of blood flow
Hypercoagulability
Changes to the blood vessel wall
Causes of VTE
Surgery/trauma Immobility Hospitalisation Malignancy HRT/OCP/pregnancy
Thrombophilia
Higher propensity to clot
Testing for inherited thrombophilia mainly focused on younger patients with spontaneous, unexplained VTE
Most common abnormality associated with familial thrombosis
Activated protein C resistance secondary to a point mutation in the factor V gene
How does the OCP affect the likelihood of thrombosis?
OCP increases the likelihood of thrombosis due to interaction with factor V Leiden, which is a variant form of factor V and increases DVT risk
Factor V Leiden
In normal coagulation, factor Va is inactivated by protein C by cleaving the factor V molecule at an Arg residue. Factor V Leiden is a mutated version of factor V which has a Glu residue instead of the Arg residue and is therefore resistant to cleavage and therefore protein C is unable to act as an anticoagulant.
Prothrombin 20210 mutation
Second most common genetic thrombophilic abnormality
Mutation in the promoter region of the prothrombin gene leading to excess production of prothrombin
Signs and symptoms of DVT
Unilateral leg pain
Swelling
Discolouration
Oedema
Signs and symptoms of PE
Shortness of breath Chest pain Tachycardia Tachypneoa Hypoxia
VTE diagnosis
Well’s score for DVT
High risk patients should be referred for radiology to exclude or confirm thrombus (ultrasound for DVT, CTPA for PE)
D-dimer test
Well’s score
More than 2 points = likely DVT, less than 2 points = unlikely DVT
1 point awarded for various criteria, including but not limited to malignancy, leg swelling, tenderness, pitting oedema, previous DVT
Heparins
Often used while waiting for the full effect of warfarin
Most often subcutaneous LMWH used because of its good bioavailability – in NZ, called enoxaparin
Accelerate inhibition of activated thrombin and Xa in plasma
Rivaroxaban
Binds and inhibits Xa
Dabigatran antidote
Idarucizumab
Rivaroxaban antidote
Xa decoy molecule
Classic triad of PE
Pleuritic pain
SOB
Haemoptysis
Febrile neutropenia
Potentially catastrophic complication of treatment of leukaemia and other cancers
Development of fever in a patient with abnormally low neutrophil granulocytes in the blood
Describe the blood tests that you would expect to see in febrile neutropenia
Total WBC count could be fine or low Blasts will generally be high Neutrophils will be very low Lymphocytes could be low or normal Platelets will be very low Haemoglobin likely to be slightly low
Tazocin
Piperacillin and tazobactam
Very broad spectrum antibiotic
Bactericidal against pretty much everything – almost all aerobic bacteria
Gentamicin
Active against almost all aerobic gram -ve bacilli
Do patients with severe neutropenia benefit from being nursed in isolation?
Studies show isolation reduces the number of days of fever but has no significant impact on overall mortality
