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haemostasis and anaemia Flashcards

1
Q

What is normal haemostasis?

A
  1. Localised vasoconstriction at injury site
  2. Platelet adhesion to vessel wall and formation of platelet aggregation/plug
  3. Coagulation cascade activation—> fibrin formation (reinforces plug)
  4. Fibrinolytic system activation which digests plug, reestablishing vascular patency
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2
Q

What are platelets?

A 
Small non-nucleated cells
Fragments of megakaryocyte cytoplasm
140-350 x10^9/l
<20- spontaneous bleeding
>80- haemostatic
Thrombocytopenia- reduced
Thrombocytosis
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3
Q

What is primary haemostasis?

A

Present w purpura, bruising, bleeding from cuts, heavy periods, surgical bleeding
~inv vessel wall, platelets and Von Willebrand factor

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4
Q

What is secondary haemostasis?

A

Present w joint and muscle haematomas and surgical bleeding, bruising not prominent
~inv coagulation cascade

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5
Q

How should a patient w a bleeding disorder be managed?

A

History- bruising? bleeding after minor injury/extractions/surgery? epistaxis? menorrhagia? family history? drugs (eg. aspirin, warfarin, cytotoxics)? alcohol?

Examination- ecchymoses? purpura? haemarthrosis? damaged joints? anaemia? signs of liver disease? splenomegaly?

Investigations- full blood count? clotting screen (PT, APTT, fibrinogen)? bleeding time/PFA?

Treatment- depends on diagnoses 
Haemophilia A- FVIII concentrate
Haemophilia B- FIX concentrate
Thrombocytopenia- platelet transfusion
Warfarin overdose- Vit K
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6
Q

What are some bleeding terms?

A 
Menorrhagia- heavy menstrual periods
Epistaxis- nose bleed
Haemoptysis- coughing blood
Haematemesis- vomiting blood
Haematuria- blood in urine
Malaena- black stool (bleed in upper GIT)
Ecchymoses- bruises
Purpura- purple blood spots
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7
Q

What does PFA stand for?

A

Automated platelet function analysis

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8
Q

What are some inherited vascular bleeding disorders?

A

Hereditary haemorrhagic telangiectasia

Ehlers-Danlos syndrome

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9
Q

What is Ehlers-Danlos syndrome?

A

V flexible joints

Stretchy and fragile skin

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10
Q

What is hereditary haemorrhagic telangiectasia?

A

Arteriovenous malformations
Regular nosebleeds
Red/purple spots/lines under skin

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11
Q

What are coagulation factor disorders?

A

Haemophilia A and Haemophilia B= x linked

Von Willebrand disease- autosomal dominant

Others- autosomal recessive, deficiciency of fibrinogen or factors II, V, VII, X, XI, XIII

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12
Q

What is the frequency of bleeding disorders?

A

Haemophilia A- 1:5000
Haemophilia B- 1:25000
VWD- 1:1000

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13
Q

What is Haemophilia?

A

A- factor VIII deficiency
B- factor IX deficiency

Identical clinical features
Sex linked inheritance

Sites of bleeding- joints, muscles, post trauma, post op

Severity-
<1%- severe
1-5%- moderate 
5-50%- mild
50%-150%- normal
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14
Q

How is haemophilia treated?

A

Mild Haem A- desmopressin (releases factor VIII from endothelium)

All severities- factor VIII/IX concentrate- UK recombinant products

Plasma derived products- risk of infection, all products virally inactivated since 1985

Haemophiliacs treated before 1985 (HIV 30%, Hep B 5%, Hep C 98%)

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15
Q

What is Von Willebrand Disease?

A

Autosomal dominant
3 main types (many subtypes)
Milder than haemophilia
Clotting factor + platelet abnormality

Sites of bleeding- bruising, cuts, gums, epistaxis, menorrhagia, post op, post trauma

Treatment-
~desmopressin (DDAVP)
~intermediate purity (plasma derived) factor VIII

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16
Q

What tests should be done for Haem A?

A

Factor VIII- low

APTT- prolonged

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17
Q

What tests should be done for Haem B?

A

Factor IX- low

APTT- prolonged

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18
Q

What tests should be done for VWD?

A

Factor VIII- low
VW factor- low
BT- Prolonged
APTT- Prolonged

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19
Q

What are some inherited platelet disorders?

A

Affecting number-
MYH-9 related thrombocytopenia
32 other inherited causes of it

Affecting function-
Glanzmann’s thrombasthenia
Storage pool disease

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20
Q

What is thrombosis?

A

Blood coagulation in a vessel

Arterial-
~high pressure, platelet rich
~eg. MI, stroke
~treat- anti platelet drugs

Venous-
~low pressure, fibrin rich
~eg. deep vein thrombosis, pulmonary embolism
~treat- anticoagulants

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21
Q

What are risk factors for venous thrombosis?

A

Acquired-
~age, previous VTE, surgery/trauma, immobility, obesity, cancer/serious illness, pregnancy, the pill, hormone replacement therapy

Inherited thrombophilia-
~antithrombin deficiency (1:3000), protein C deficiency (1:300), protein S deficiency (1:300), factor V Leiden mutation (1:20), prothrombin G20210A condition (1:75)

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22
Q

What are risk factors for arterial thrombosis?

A

Smoking, obesity, hypertension, diabetes mellitus, older age

Not inherited

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23
Q

What are some aquired vascular bleeding disorders?

A 
Senile purpura
Scurvy (Vit C deficiency)
Steroid purpura (long term use)
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24
Q

What are causes of thrombocytopenia?

A

Failure to produce-
~Vit B12 or folate deficiency
~disease infiltrates bone marrow
~radiation, cytotoxic therapy

Increased consumption-
~immune thrombocytopenia
~disseminated intra vascular coagulation
~HIV infection

Hypersplenism

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25
What is immune thrombocytopenia?
Children- usually follows acute infection, self limiting so not treated Adults- unclear cause, chronic, treat if bleeding Diagnosis- exclude other causes of thrombocytopenia, bone marrow exam Treatment- steroids, IV immunoglobulin, splenectomy, thrombopoietin receptor analogues
26
What is desseminated intravascular coagulation (DIC)?
Breakdown of haemostatic balance Simultaneous bleeding and micro vascular thrombosis Life threatening Causes- sepsis, obstetrics, malignancy Treat- remove cause, give plasma/platelets if bleeding
27
What is the platelet distribution like in a person w splenomegaly?
Normal- 30% spleen, 70% circulating Splenomegaly- 60-90% spleen, 10-40% circulating
28
What are some aquired platelet function abnormalities?
Antiplatelet drugs- aspirin, Clopidogrel, prasugrel- irreversible action (prasugrel more rapid and consistent inhibition than Clopidogrel) Renal disease- increased bleeding(anaemia, thrombocytopenia/uraemia/treat w desmopressin or dialysis)/thrombotic risk (nephrotic syndrome- aquired antithrombin deficiency) Liver disease (reduced clotting factors, hypersplenism, portal hypertension, dysfibrinogenemia, increased fibrinolysis) DIC
29
What happens with a Vit K deficiency?
Vit K synthesises factors II, VII, IX, X Fat soluble vitamin Must have shot at birth due to deficiency Obstructive jaundice- narrowed/blocked bile duct Maifests as prolonged PT Vit K given via IV
30
What drugs may be the causes of aquired bleeding disorders?
Antiplatelet drugs (aspirin) Anticoagulants (heparin/warfarin) Steroids- tissues thin causing bleeding/bruising Drugs affecting liver, kidneys, bone marrow
31
What are some antiplatelet drugs?
Aspirin Clopidogrel Prasugrel Ticagrelor
32
What are some anticoagulants?
IV- unfractionated heparin Subcutaneous- low molecular weight heparin Oral- warfarin, dabigatran, rivaroxaban*, apixaban*, edoxaban, vit K antagonists* (96% warfarin, 4% acenocoumarol) *used more over other oral
33
What is heparin?
``` Glycosaminoglycan Binds to antithrombin and increases its activity Indirect thrombin inhibitor Not absorbed via gut Continuous infusion Monitor w APTT ``` Low molecular weight- less variation in dose, weight adjusted dose, once daily, Renault excreted, for treatment and prophylaxis
34
What is warfarin?
99% plasma protein bound Inhibits II, VII, IX, X Peak effect- 3-4 days after start 4-5 days after stop- still affected Side effects- bleeding, embryopathy Measured by INR Dose based on INR For DVT/PE- 2-3 dose Freq of monitoring depends on stability of INR, must be measured before surgery
35
Why are direct oral anticoagulants advantageous?
``` Oral No monitoring Standard dosing No alcohol/food interactions V few drug interactions Short half life (10-15hrs) ``` However, more expensive than warfarin
36
What is vaccine induced immune thrombosis and thrombocytopenia?
``` 4-16 days after Astra Zeneca 18-65 years Cerebral or portal vein thrombosis Thrombocytopenia 1:100000 25-30% mortality ```
37
What is anaemia?
Haemoglobin conc below normal range Males- <125g/l Females- <115g/l
38
How is the normal haemoglobin range measured?
Measure Hb in normal range Work out mean and SD Normal range is mean +/- 2SD Different in men and women
39
What are symptoms of anaemia?
Fatigue, reduced exercise tolerance, shortness of breath Postural hypotension, dizziness, palpitations Angina Heart failure
40
What are signs of anaemia?
``` Pallor Tachycardia Heart murmurs Koilonychia- iron deficiency (dish shaped nails, brittle, soft) Angular stomatitis Glossitis- B12/folate deficiency ```
41
How do you diagnose anaemia?
Full blood count- ~Haemoglobin and it’s mean cell volume ~White cell count ~Platelet count
42
What is a normal mean cell volume?
82-96 fl Anaemia- Microcytic- <82 Normocytic- 82-96 Macrocytic- >96
43
What causes microcytic anaemia?
Due to iron deficiency, thalassaemia (inherited RBC disorder) or anaemia of chronic disease (rarely)
44
What causes macrocytic anaemia?
Due to Vit B12/folate deficiency Macrocytosis w/o anaemia- ~liver disease ~hypothyroidism ~alcohol
45
What causes normocytic anaemia?
Acute bleeding Congenital/acquired haemolysis (RBCs destroyed) Aplastic anaemia (RBCs not produced in marrow) Anaemia of chronic disease
46
What causes iron deficiency?
Reduced intake (rare in UK) Increased requirements in pregnancy/childbirth/malabsorption/coeliac disease Chronic blood loss- menorrhagia/GI blood loss (due to oesophageal web?- Patterson-Kelly syndrome)
47
How do you diagnose iron deficiency?
Full blood count- Reduced Hb and MCV Serum Ferritin- blood test Bone marrow/liver biopsy- to see tissue iron stores
48
How do you investigate iron deficiency?
History- bleeding somewhere? Black stool? Stool consistency? Appetite? Weight loss? Abdominal pain? Freq/clots/attendance barrier of periods? Examination- lymph nodes? masses in abdomen? rectal examination? Ferritin Gastroscopy/colonoscopy- ulcers? Polyps?
49
How do you treat iron deficiency?
Treat cause | Ferrous sulphate 200mg oral daily, until Hb normal and then 3 months to rebuild stores
50
What is B12 and folate deficiency?
Needed for haematopoiesis/DNA synthesis of all cells Deficiency causes magaloblastic anaemia- precursors of RBCs become really large in marrow ~macrocytic anaemia (high MCV) ~leukopenia ~thrombocytopenia
51
How do we get B12?
Dietary- bacteria/animal products Absorption- intrinsic factor from stomach binds w B12 and is absorbed in terminal ileum as complex (intrinsic factor produced by parietal cells) Body storage- 4 years
52
What causes B12 deficiency?
Lack of intrinsic factor Pernicious anaemia (autoimmune disorders- antibodies prohibit binding between intrinsic factor and B12) Gastrectomy Failure of absorption in terminal ileum due to resection, Crohns, TB, lymphoma etc Diets- vegans?
53
What happens if someone has B12 deficiency?
``` Macrocytic anaemia Megaloblasts in marrow Pancytopenia- low Hb, WBCs and platelets Affects all body cells Neuropathy- memory loss? Altered personality? Dementia? Peripheral neuropathies? Ataxia? ```
54
What is pernicious anaemia?
Autoimmune disorder Usually affects elderly Achlorhydria- absence of hydrochloric acid in gastric secretions Autoantibodies against intrinsic factor- blocks binding Associated w other autoimmune disorders- hypothyroidism, vitiligo
55
How is B12 deficiency diagnosed?
Serum B12- blood test In pernicious anaemia- ~intrinsic factor antibodies (50%) ~parietal cell antibodies (80%)
56
How is B12 deficiency treated?
``` Parenteral hydroxycobalamin- intramuscular, 1mg every 2 days initially Give before folate if also deficient Reticulocyte (young RBC) response Risk of hypokalaemia- monitor potassium 1mg every 3 months for life ```
57
How do we get folate?
Dietary- fresh fruit/veg Absorbed in proximal intestine Low body stores- easily depleted Need 100micrograms
58
What causes folate deficiency?
Dietary Malabsorption- coeliac disease Increased requirements- pregnancy, haemolysis, some drugs (eg. Folate antagonists)
59
How is folate deficiency treated?
Oral folate 5mg tablet daily | Works for all causes inc malabsorption
60
What are haemolytic anaemia?
HEREDITARY ~RBC membrane defect eg. Hereditary spherocytosis ~Abnormal RBC metabolism eg. G6PD/pyruvate kinase deficiency ~Hb abnormalities eg. Sickle cell disease ACQUIRED ~Auto/allo-immune eg. Rhesus disease ~RBC fragmentation syndromes ~infections
61
What do sickle cell disease?
Autosomal recessive Afro-Caribbean population Single point mutation. (Alanine changes to thymine) Heterozygous patients protects from malaria Painful vaso-occlusive sickle cell crises Crises precipitated by infection/cold/hypoxia etc Diagnose- FBC, sickle cell test and Hb electrophoresis

basic oral and dental care (49 decks)

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