coagulation Flashcards
(215 cards)
1
Q
The process by which a blood clot forms to reduce
blood loss after damage to a blood vessel
A
coagulation
2
Q
group of diseases caused by deficiency of clotting factors which may lead to defects in normal clot formation process
A
Coagulation disorder
3
Q
A process by which the body repairs damage to a blood vessel to
prevent hemorrhage
A
Hemostasis
4
Q
Two general steps of hemostasis
A
- platelet plug formation
- fibrin clot formation
5
Q
At the site of injury, a hemostatic plug is formed by the interaction of the blood vessels, platelets and coagulation factors
A
Platelet plug formation
6
Q
As the plug is formed, the coagulation system generates thrombin from prothrombin, initiating fibrin clot formation
A
Fibrin clot formation
7
Q
Process of hemostasis
A
- injury
- vascular spasm
- platelet plug formation (primary hemostasis
- coagulation cascade (secondary hemostasis)
8
Q
A blood vessel is severed. Blood and blood components (e.g., erythrocytes, white blood cells, etc.) are leaking out of the breaks.
A
Injury
9
Q
The smooth muscle in the vessel wall contracts near the injury point, reducing blood loss.
○ inflammation
A
vascular spasm
10
Q
Platelets are activated by chemicals released from the injury site and by contact with underlying collagen. The platelets become spiked and stick to each other and the wound site.
A
Platelet plug formation (Primary Hemostasis)
11
Q
In coagulation, fibrinogen is converted to fibrin, which forms a mesh that traps more platelets and erythrocytes, producing a clot.
A
Coagulation Cascade (Secondary Hemostasis
12
Q
Contact Activation Pathway
A
Intrinsic pathway
13
Q
Tissue factor pathway
A
extrinsic pathway
14
Q
Factor X
A
Final common pathway
15
Q
if there is a presence of damage, Factor XI will become XIa → activation of IX to IXa, with VIIIa → activation of X to Xa
A
Intrinsic pathway
16
Q
Factor III to IIIa → activation of VII and VIII → combine with III to activate Factor X to Xa → activation of Va → Prothrombin → thrombin → fibrinogen → fibrin
A
Extrinsic pathway
17
Q
surface damage
A
Intrinsic pathway
18
Q
in trauma + inflammation
A
extrinsic pathway
19
Q
Initiated through the activation of two separate pathways of intrinsic and extrinsic pathways
A
Coagulation cascade
20
Q
both pathways lead to the production of ________________ which marks the beginning of the common pathway of coagulation leading to cloth formation
A
Factor X
21
Q
● Extrinsic pathway first, then intrinsic pathway
● Amplify the coagulation process
A
cross-activation
22
Q
● Also known as Coagulation Factors
● Prompt reactions that activates more clotting or coagulation factors
A
Clotting factors
23
Q
● Secreted primarily by the _____ and the ________
(Clotting factors)
A
liver and platelets
24
Q
Vitamin K deficiency leads to:
A
bleeding
25
● The liver requires _________ as a co-factor to produce clotting factors
(Clotting factors)
Vitamin K
26
There are ____ clotting factors
12
27
There is no factor _____; it is not used already
VI
28
Inactivated forms:
(Clotting factors)
I, II, III
29
Activated forms:
Ia, IIa, IIIa
30
VI is identical to V (t or f)
T
31
Pathways are dependent to:
Clotting factors, calcium ions, and vitamin K
32
○ activated by damage directly to the blood vessels and exposure to collagen and circulating platelets in blood
Intrinsic pathway
33
○ activated by tissue damage, malignancy, inflammation, sepsis
Extrinsic pathway
34
Fibrinogen
I
35
Prothrombin
II
36
Tissue thromboplastin or tissue factor
III
37
Calcium ions
IV
37
Proaccelerin; labile factor
V
38
Antihemolytic factor A
VIII
39
Not used
VI
40
Proconvertin; stable factor
VII
41
Antihemolytic factor B (plasma thromboplastin component); Christmas factor
IX
41
Hageman factor
XII
42
Fibrin-stabilizing factor
XIII
42
Stuart-Prower factor (thrombokinase)
X
43
antihemolytic factor C (plasma thromboplastin antecedent)
XI
44
Common; converted into fibrin
I
45
Extrinsic (1)
Tissue thromboplastin/ tissue factor
46
Common; converted into thrombin
II
46
Extrinsic and Intrinsic (1)
V
47
entire process
IV
47
Not used
VI
48
Extrinsic (2)
Proconvertin
49
Intrinsic; deficiency results in hemophilia A
VIII
50
Intrinsic; deficiency results in hemophilia B
IX
51
Extrinsic and intrinsic (2)
X
52
Intrinsic; deficiency results in hemophilia C
XI
53
Intrinsic; initiates clotting in vitro also activates plasmin
XII
54
Stabilizes fibrin; slows fibrinolysis
XIII
55
Risk factors for Coagulation disorders
- age
- family history and genetics
- medical conditions
- medications
- sex
56
______ are more likely to develop Vit K deficiency
newborns
57
risk factors medications
● antibiotics
● blood thinners
● anticoagulants
58
● blood transfusion
● bowel diseases (IBD) or bowel surgery
● cancer
● congenital heart disease
● hypothyroidism
● some autoimmune diseases
medical conditions
59
Sex: congenital hemophilia
males
60
acquired hemophilia during and after pregnancy
females
61
Signs and symptoms of coagulation disorders
● Blood in urine or stool
● Excessive bleeding
● Frequent, large bruises
● Heavy bleeding after giving birth
● Heavy menstrual bleeding
● Petechiae
● Redness, swelling, stiffness or pain
● Umbilical stump bleeding
62
○ Does not stop even after applying pressure
○ Spontaneous bleeding
■ Nose bleed
■ Bleeding after dental procedure or surgery
● Excessive bleeding
63
○ More than 7 days or change of sanitary pads every hour
● Heavy menstrual bleeding
64
○ Bleeding under the skin causing tiny spots
○ Violet or brown
Petechiae
65
○ Bleeding after 1-2 weeks after the umbilical cord was cut
Umbilical stump bleeding
66
Complications
● Bleeding in the brain or CNS
○ Hemorrhagic stroke
● Bleeding in the throat
○ Inflammation → swelling → DOB
● Bleeding into the abdomen
● Damaged joints
● Hard masses in the bones
● Miscarriages
67
Diagnosis
- CBC
- PTT
- PT
- Mixing test
- vWF
- Clotting factor test
- Bethesda test
- Factor XIII antigen and activity assays
- Genetic testing
68
● measure different parts of the blood and identify the number of blood cells and platelets
CBC
69
● how long it takes for blood to clot by determining the clotting factors involved
PTT
70
● same with PTT but also measures the clotting factors not covered by PTT
PT
71
PTT measures
Intrinsic
72
PT measures
Extrinsic
73
● identify whether the bleeding is caused by antibodies blocking the functions of the clotting factors
● If autoimmune
Mixing test
74
● measure the amount of vWF and if these factors are working correctly
von Willebrand factor (vWF) tests
75
● determine if clotting factors are absent or present below normal levels
Clotting factor tests
76
● to check for antibodies for Factors XIII and IX
Bethesda test
77
● Factor XIII deficiency
Factor XIII antigen and activity assays
78
● to identify if genes are responsible for coagulation disorders
Genetic testing
79
platelet function analyzer
PFA-100
80
Laboratory Monitoring
- Activated Partial Thromboplastin Time (aPTT)
- Prothrombin Time (PT)
81
● Test for intrinsic and common pathways
● Dependent on activity of all coagulation factors, except for Factors VII and XIII
aPTT
82
- 30 to 40 seconds
● Monitor heparin treatment and screen for hemophilia
● Integrity of intrinsic system (incl. XII, XI, VIII and IX)
● Liver disease decrease the production of these factors because liver is the main source
aPTT
83
● Test for extrinsic pathway activity and common pathways (VII, V, X, prothrombin and fibrinogen)
● Measures Vitamin K-dependent factors activity (Factors II, VII, IX, and X)
PT
84
- 10 to 14 seconds
● Thromboplastin + Calcium to plasma = clotting time
● Liver disease and warfarin therapy
● Liver is the site of synthesis of plasma clotting factors
PT
85
aPTT is dependent on all coagulation factors except:
VII and XIII
86
PT: Test for extrinsic pathway activity and common pathways namely:
VII, V, X, prothrombin and fibrinogen
87
PT: measures Vitamin K-dependent factors activity namely:
II, VII, IX, and X
88
components measured of Bleeding Time:
Platelet function
Vascular integrity
89
components measured of PT
I, II, V, VII, IX, X
90
components measured of PTT
I, II, V, VIII, IX, X, XI,
XII
91
components measured of thrombin time
I, II
92
normal values of bleeding time
3 to 10 mins
93
normal values of PT
10 to 14 secs
94
Classification of Clotting Disorders
- Congenital
- acquired
94
normal values of PTT
30 to 40 secs
95
normal values of thrombin time
12-20 secs
96
Congenital
- hemophilia A
- hemophilia B
- von Willebrand's disease
97
○ A deficiency of factor VIII, inherited as an x-linked recessive trait affecting males, females being the carriers
hemophilia A
98
Acquired
- secondary to drugs
- disease related
99
○ The second most common inherited bleeding disorder after vWD
hemophilia A
100
Males
(Hemophilia A)
hemizygous
101
Females
(hemophilia A)
heterozygous
102
○ Caused by a mutation of the factor IX gene, leading to factor IX deficiency
hemophilia B
103
○ The second most common form of hemophilia, rarer than hemophilia A
hemophilia B
104
Hemophilia B is also called:
royal blood's disease
105
Acquired: Disease-related
Liver disease, vitamin K deficiency, disseminated intravascular coagulation (DIC), fibrinolytic disorders
105
Acquired: secondary to drugs
heparin, coumarin
106
○ Microvascular and macrovascular clotting and compromised blood flow that is a rare but serious condition that causes abnormal blood clotting throughout the body’s blood vessels
Disseminated intravascular coagulation
107
An inherited X-linked recessive and lifelong blood disorder where an essential blood clotting factor is either partly or completely missing
Hemophilia
108
Hemophilia A is linked to level of ____________
Factor VIII
109
1% _________ Hemophilia A
severe
110
1%-5% __________ Hemophilia A
moderate
111
6% - 30% _________ Hemophilia A little risk of spontaneous bleeding
Mild
112
Management of Hemophilia
Factor replacement therapy
113
● Main treatment of hemophilia
● Clotting factors from donations or made in the laboratory
Factor replacement therapy
114
Concentrates of clotting factor VIII (for hemophilia A) or clotting factor IX (for hemophilia B) are slowly dripped or injected into a ________
vein
115
Plasma-derived Factor Concentrates
- cryoprecipitate and fresh frozen plasma (FFP)
116
FFP: 250 - 300 mL, Cryoprecipitate:
(volume)
Cryoprecipitate: 10-20mL
117
FFP: 30 minutes, Cryoprecipitate:
(time to prepare)
Cryoprecipitate: 30 minutes
118
FFP: All, including factors II, VII, VIII, IX, X, XI, and vWF, Cryoprecipitate:
(other coagluation factors)
Cryoprecipitate: Factors VIII, XIII, and vWF
119
FFP: 700 - 800 mg, Cryoprecipitate:
(Fibrinogen)
Cryoprecipitate: 150 - 250 mg
120
○ Developing antibodies (proteins) that attack the clotting factor
○ Developing viral infections from human clotting factors
○ Damage to joints, muscles, or other parts of the body resulting from delays in treatment
Complications of Replacement Therapy:
121
○ Very expensive, often to be imported
○ High risk of contamination with hepatitis B virus, hepatitis C virus, and HIV from the large number of donors
Problems with treatment with commercial factor VIII concentrate
122
○ Recombinant Factor VIII concentrate, which does not come from human plasma
○ Genetically engineered using DNA technology and commercially prepared factor concentrates treated to remove or inactivate blood-borne viruses
○ No plasma or albumin, does not spread blood-borne viruses
Recombinant Factor Concentrates
123
● FRT not needed; Desmopressin acetate may be given to raise the body’s level of Factor VIII
Mild hemophilia
● Mild or no risk of spontaneous bleeding
124
● FRT given at home two or three times a week; Preventive therapy usually is started in patients at a young age and may need to continue for life
Severe hemophilia
- maintenance
124
● FRT only when bleeding occurs or to prevent bleeding that could occur when doing certain activities
Moderate Hemophilia
- only if there is bleeding
125
● also known as ACE 910 or Emicizumab
Hemlibra
126
Other treatment options:
- Hemlibra
- DDAVP or Stimate (Desmopressin Acetate)
- Amicar
126
● Desmopressin Acetate
DDAVP or Stimate (Desmopressin Acetate)
127
● Epsilon Amino Caproic Acid
Amicar
128
● It works by replacing the function of factor VIII, rather than replacing the missing clotting factor VIII directly
Hemlibra
129
● These are medications that are similar to a hormone that occurs naturally in the body. The medications release factor VIII from where it is stored in the body tissues.
● Give ____________ for mild ONLY
○ Not FRT immediately, only for moderate and severe
DDAVP or Stimate
130
● Medication that can be given through a vein or by mouth (as a pill or a liquid)
● It prevents blood clots from breaking down, resulting in a firmer clot, and is often used for bleeding in the mouth or after a tooth has been removed because it blocks a substance found in the saliva that breaks down clots.
Amicar
130
New Hemophilia Agents: Treatment for Hemophilia A
- Eloctate
- Obizur
- Nuwiq
- Kovaltry
- Afstyla
131
New hemophilia Agents: Treatment for Hemophilia B
- Rixubis
- Alprolix
- Idelvion
132
● Approved June 2014
● Factor VIII recombinant; Fe fusion protein
Eloctate
133
● Approved October 2014
● Recombinant
Obizur
134
● Approved September 2015
● Recombinant factor VIII
Nuwiq
135
● Approved March 2016
● Recombinant
● Use infusion line provided with product as it has in-line filter
Kovaltry
136
● Approved May 2016
● Recombinant
Afstyla
137
● Approved March 2014
● Recombinant; Fe fusion protein
Alprolix
138
● Approved June 2013
● Recombinant factor IX
Rixubis
139
● Approved March 2016
● Recombinant; albumin fusion protein
Idelvion
140
Priorities in hemophilia treatment and care include:
1. prevention of bleeding and joint damage
2. prompt management of bleeding episodes including physical therapy and rehabilitation after joint bleeds
3. pain management
4. management of musculoskeletal complications
5. prevention and management of inhibitors
6. management of comorbidities
7. dental care
8. quality-of-life assessments and psychosocial support
9. genetic counselling and diagnosis
10. ongoing patient/family caregiver education and support
141
● Acute bleeds should be treated __________________
(Principal care)
as quickly as possible
142
- Desmopressin administration can raise FVIII level ______________________ to control
bleeding
adequately (3 to 6 times the baseline level)
143
● ________ and ________ should be avoided
- could prolong bleeding, as it also inhibits platelet formation
○ Use paracetamol instead
ASA and NSAID
144
● _____________ prevents periodontal disease and dental caries, which predispose to gum bleeding
Good oral hygiene
145
General recommendations
- Prophylaxis with clotting factor concentrates (CFCs)
- Episodic replacement therapy
146
● Regular replacement therapy or the regular intravenous (IV) infusion of the missing clotting factors
● FVIII in hemophilia A and FIX in hemophilia B
Prophylaxis with clotting factor concentrates (CFCs)
147
- On-demand therapy, the administration of CFCs only at the time of a bleeding episode
Episodic replacement therapy
148
● _____________ is the standard of care for people with severe hemophilia, and for some people with moderate
hemophilia
(WFH Recommendations)
Prophylaxis
148
● Both_____________ and _____________, as well as other hemostasis products when
appropriate, can be used for treatment of bleeding and prophylaxis in people with hemophilia
(WFH Recommendations)
virus-inactivated plasma-derived and recombinant CFCs
149
● The use of cryoprecipitate can only be justified in situations where _________________________ as there is no proven advantage for their use over CFCs
(WFH Recommendations)
clotting factor concentrates are not available
150
● It is strongly encouraged that _________________ procedures be used, if available
(WFH Recommendations)
viral-inactivation
151
● 1-deamino-8-D-arginine vasopressin
● Synthetic analogue of vasopressin that boosts plasma levels Factor VIII and vWF
Desmopressin (DDAVP)
152
● May be the treatment of choice for patients with mild or moderate hemophilia A when Factor VIII can be raised to an appropriate therapeutic level
Desmopressin (DDAVP)
153
Serious sites of bleeding in hemophilia
- Joints
- Muscles, especially deep compartments (iliopsoas, calf, forearm)
- Mucous membranes of the mouth, nose, and genitourinary tract
154
Frequency of bleeding sites: 70% - 80%
Joints
- more common in hinged joints; ankles knees, elbows
- less common in multi-axial joints; shoulders, wrists, hips
154
Life-threatening
- Intracranial
- Neck/throat
- gastrointestinal
155
Frequency of bleeding sites: 10% - 20%
Muscles
156
Frequency of bleeding sites: 5% - 10%
Other sites, major bleeds
157
Frequency of bleeding sites: <5%
CNS
158
People with hemophilia with a ______ or _________ bleed, the WFH recommends following the PRICE principles in addition to increasing factor levels
muscle or joint bleed
159
PRICE
- Protection
- Rest
- Ice
- Compression
- Elevation
160
● Reduce weight bearing or stress on the affected joint or muscle by using crutches or other supports such as a 'collar and cuff' for the arm
● Avoid putting weight on the affected side completely for the first 48 hours and possibly longer if it is a severe bleeding
Protection
161
● The affected area should initially be rested completely, generally for the first 24 to 48 hours depending on the severity of the bleeding episode to allow the swelling to go down and prevent further bleeding
● The injured area should not be forced into any position
● ‘Rest' is not the same as 'immobility', too much rest can also be damaging, so start to move the joint gently, as pain allows, within one or two days of treatment
Rest
162
● Reduces swelling, and therefore pain
● If the muscle or joint is very swollen, wait a day or so before using a compression bandage and then apply as
pain allows
● Nurse or physiotherapist can provide an elasticated bandage, make sure it fits correctly as additional damage can be caused where the bandage is too tight
● Try not to allow wrinkles in the bandage and make sure to remove it at night before you go to sleep
Compression
162
● Helps reduce swelling, prevent further bleeding, and eases pain
● Use a gel cold pack or an ice pack from a bag of frozen peas or crushed ice wrapped in a cloth
● Cold wraps or packs should be applied to the affected area for around 10 to 15 minutes every 2 hours or so
● Continue using ice for several days after the bleed if joint is still warm and swollen
● Do not apply for more than 20 minutes at a time
● Do not place ice directly on the skin as it can burn
Ice
163
● Helps reduce swelling and relieve pain by increasing the blood flow away from the injured area
● The injured area should be raised above the level of the heart
● When elevating leg, remove the compression stocking to allow normal, healthy circulation.
● Elevate ‘little and often’ for around 20 minutes at a time
Elevation
164
For people with hemophilia, the WFH recommends the use of antifibrinolytic drugs (____________________) alone or as adjuvant treatment, particularly in controlling mucosal bleeds and for invasive ___________
tranexamic acid, epsilon aminocaproic acid [EACA]; dental procedures
165
● An antifibrinolytic agent
● Competitively inhibits the activation of plasminogen to plasmin
● Promotes clot stability
Tranexamic acid
166
● ________________ for some types of hemophilic bleeding
(Tranexamic acid)
Adjunctive therapy
167
● Useful for treating superficial soft tissue and mucosal bleeds (_________________)
(Tranexamic acid)
oral bleeding, epistaxis, and menorrhagia
168
● Brand name:
(Tranexamic acid)
Hemostat
169
Paracetamol/acetaminophen: if not effective
(pain management)
Switch to
- COX 2 inhibitors (celecoxib, meloxicam, nimesulide, and others)
- Paracetamol/ acetaminophen plus codeine (3-4 times a day)
- Paracetamol/acetaminophen plus tramadol (3-4 times a day)
170
use a slow release product with an escape of a rapid release. Increase the slow release product if the rapid release product is used more than 4 times/day
(pain management)
Morphine
171
should be used with caution in patients with hypertension and renal dysfunction (paint management)
COX-2
172
○ Regular high-dose infusions of Factor VIII and Factor IX
○ Demanding and costly but provides 60-80% success chance
immune tolerance induction (ITI) therapy
173
Eradication of inhibitors is currently best achieved through:
(Management of patients with inhibitors)
immune tolerance induction (ITI) therapy
174
● For patients with hemophilia A with an inhibitor, the WFH recommends that ______________ should be used for regular prophylaxis in addition to clotting factor concentrates (CFC)
emicizumab
175
Mild - moderate
(Factor Requirement Calculations)
- soft tissue
- muscles
- hemarthrosis epistaxis
176
Severe
(Factor Requirement Calculations)
- CNS
- GI
- Neck/throat
177
Up to 100%
(Factor Requirement Calculations)
Severe
178
Up to 50%
(Factor Requirement Calculations)
Mild- moderate
179
Type of Bleeding Episodes:
Early hemarthrosis, minor muscle or oral bleeding
(Desired Factor VIII Increase)
Mild
180
Type of Bleeding Episodes:
Muscle bleeding, bleeding into the oral cavity or mild head trauma
(Desired Factor VIII Increase)
Moderate
181
Type of Bleeding Episodes:
Life or limb threatening hemorrhage, GI bleeding, intracranial, intra-abdominal or intrathoracic bleeding, fractures
(Desired Factor VIII Increase)
Major
182
FVIII Level Required and Frequency:
- 20 to 40
- 12 to 24 hrs
(Desired Factor VIII Increase)
Mild
183
FVIII Level Required and Frequency:
- 30 to 60
- 12 to 24 hrs
(Desired Factor VIII Increase)
Moderate
184
FVIII Level Required and Frequency:
- 60 to100
- 8 to 24 hrs
(Desired Factor VIII Increase)
Major
185
Duration (Days):
At least 1 day until bleeding resolution is achieved
(Desired Factor VIII Increase)
Mild
186
Duration (Days):
Until pain and acute disability are resolved (around 3 to 4 days)
(Desired Factor VIII Increase)
Moderate
187
Duration (Days):
Until resolution of bleed (around 7 to 10 days)
(Desired Factor VIII Increase)
Major
188
Type of Surgery:
Including tooth extraction
Minor
189
Type of Surgery:
Intracranial, intraabdominal or
intrathoracic, or joint replacement
surgery
Major
190
● The most common bleeding disorder
● It is carried on chromosome 12 and occurs equally in men and women
● A blood disorder in which the blood does not clot properly
● A genetic disorder caused by missing or defective von Willebrand factor (vWF), a clotting protein
von Willebrand Disease (vWD)
191
● VWF binds to _________, a key clotting protein, and platelets in blood vessel walls, which help form a platelet plug during the clotting process
factor VIII
192
Blood contains many proteins that help the body stop bleeding, one of these proteins is called
von Willebrand factor (vWF)
193
● Important role in primary hemostasis
● Binds platelets
● Binds endothelial components
● Forms adhesive bridge b/w platelets and vascular subendothelial structures
● Contributes to fibrin clot formation (carries factor VIll)
Von Willebrand Factor (VWF)
194
Treatment for vWD
Desmopressin (DDAVP)
195
● Treatment of acquired hemophilia A
● Approved October 2014
● Recombinant
Obizur
195
● Treatment of acquired hemophilia A
● Approved June 2014
● Factor VIII recombinant; Fe fusion protein
Eloctate
196
● Treatment and prophylaxis of hemophilia A
● Approved September 2015
● Recombinant factor VIII
Nuwiq
197
● Treatment of hemophilia A
● Approved May 2016
● Recombinant
Afstyla
197
● Treatment of hemophilia A
● Approved March 2016
● Recombinant
● Use infusion line provided with product as it has in-line filter
Kovaltry
198
● Prophylaxis and control of hemophilia B
● Approved June 2013
● Recombinant factor IX
Rixubis
199
● Treatment of hemophilia B
● Approved March 2014
● Recombinant; Fe fusion protein
Alprolix
199
● Treatment of hemophilia B
● Approved March 2016
● Recombinant; albumin fusion protein
Idelvion
