4. Bleeding Disorders Flashcards
Introduction
Bleeding- common in dentistry
____ patients in a dental clinic will have a form of bleeding disorder
Little to no clinical risk in most patients
____ risk group – bleeding alteration from
disease or drugs
Important to diagnose prior to initiating treatment- helps prevent fatalities
• It’s important that you expect the risk. You want to prevent fatalities from happening. Or you want to prevent ____ periods of treatment.
1 in 20
high
prolonged
Recognizing patients with bleeding disorders
History taking
____ and Surgical hx Medication list
Personal and Family hx
____ hx
ROS
Easy ____ or bruising Nose bleeds
____ bleeds
• Little things like ____, NSAIDs, ____ are medications that increase the risk of bleeding. You want to know these medications***
• As you take your family history, you want to ask, “Any bleeding disorders in the family?
◦ “Any dads, uncles, grandpas with a bleeding history” when you’re thinking of Recessive X-
linked disorders.
◦ When its a female–> you want to ask “Do you have irregular or heavy bleeds during your
____ cycle?” You’re trying to rule out a bleeding disorder when you ask this.
medical
gyn
bleeding
gingival
aspirin
warfarin
menstrual
Recognizing patients with bleeding disorders
Clinical Examination – ____, ecchymoses
observation of excessive bleeding after a surgical procedure
For major invasive surgical procedures all patients should be screened for platelet ____, aPTT, ____, TT
petechiae
count
PT
Hemostasis
Primary phase
____ phase
____ phase
Secondary phase
____ phase
____ phase- where clot is dissolved
vascular
platelet
coagulation
fibronlytic
- These are your endothelial cells of your blood vessel.
- So now you have an injury (breach to epithelium). Blood wants to come out this way.
• Blood vessels will constrict to prevent further blood loss. ◦ That’s termed the “____ Phase of Hemostasis”
• In the blood flowing through the vessels, platelets will aggregate where you have a breach in the epithelium. In the presence of von Willebrand Factor (vWF, helps the platelets adhere together and to the wall of your blood vessel), you have the formation of a temporary Platelet Plug.
◦ This is termed the “____ Phase of Hemostasis”
• Your blood is not flowing out anymore. But this temporary plug is not stable nor solid, so it can easily be ____.
• You have clotting factors also within the blood that is flowing. They go through the Clotting Cascade (described in the next slide) and end up forming a ____ in the area where your temporary plug is. That forms a more stable clot.
◦ This is termed the “____ Phase of Hemostasis” where you have coagulation factors coming in and forming the Fibrin Mesh.
• At the end of this, after the Fibrin Mesh has been formed, the final process is to repair the vessel. Once the vessel is repaired, you don’t need the platelet plug/clotting factors anymore. The clot breaks down and that ends your hemostasis process.
◦ This is termed the “____ Phase of Hemostasis”
◦ She wants us to remember this, the fact that ____ breaks down your clot
vascular
platelet
dislodged
fibrin mesh
coagulation
fibrinolysis
fibrinolysis
• For the instrinsic pathway, you have Factor ____ that becomes activated and actives Factor ____. Becomes activated, actives Factor ____. Becomes actived, activates Factor ____.
◦ Remember, I skipped Factor 10 somehow. It didn’t get lost. It’s a member of the ____ pathway.
• For the extrinsic pathway, you have ____ that becomes activated and activates Factor ____. Becomes activated, activates Factor ____.
◦ So both instrinsic and extrinsic pathway come together when Factor 10 is activated to form the Common Pathway.
12 11 9 8 common
tissue factor
7
10
- When Factor 10 is activated (Common Pathway) in the presence of [____, Factor 5, ____], you have ____ activated. When Thrombin is activated, it activates ____, which ends up forming your Fibrin Clot. This is only one process of forming Fibrin Clots.
- Another process of forming Fibrin Clots is actually Factor 2 (____) which directly activates Thrombin, and this also would end up giving you the Fibrin Clots.
• So 2 processes are occuring here to get your Fibrin Clot.
◦ 1) The ____ cascade through the instrinsic & extrinsic pathway forming the Common Pathway
◦ 2) From ____ forming Thrombin which activates Fibrinogen to form Fibrin.
calcium
lipids
thrombin
fibrinogen
prothrombin
coagulation
prothrombin
• For the intrinsic pathway, the lab study we carry out to know if a disorder is coming from this pathway is
____
• For the extrinsic pathway, it’s ____ or ____ which tells you the PT based on standardized values so you don’t get different numbers in different geographic locations.
◦ INR= ____
◦ So if you have a standard or mean INR, and you take the average of your INRs from the different laboratories (around the world), and you divide by this [Standard Normal Prothrombin Time], you should
always get the same INR.
◦ So you can have different PT’s from the patient, but when you divide by the [Standard Normal
Prothrombin Time], you should always end up with the same INR number.
◦ The normal value of a patient without a bleeding problem is 1.0.
activated partial thromboplastin time (aPPT)
prothrombin time (PT)
INR
PT / [standard normal prothrombin time]
Vitamin k dependent clotting factors Factor \_\_\_\_ Factor \_\_\_\_ Factor \_\_\_\_ Factor \_\_\_\_
II
VII
IX
X
What are bleeding disorders?
Conditions that affect:
Blood vessels ____
____ production/function ____ factors
- Bleeding disorders are disorders that could affect the Vascular Phase, Platelet Phase, Coagulation Phase, or Fibrinolytic Phase of Hemostasis.
- When you talk about Vascular Phase disorder, it could be a problem with the ____ wall itself or a problem with the connective tissue.
• When you talk about Platelet Phase, it could be a problem with ____ of platelets. If you have a low # of platelets, you have an increased risk of bleeding. You can also have problems with the function of the platelets.
◦ Remember when I mentioned ____ Factor? I said that it helps with platelet aggregation and adherence of the platelets to the wall of the endothelium.
◦ So I might have an adequate # of platelets, but if some of the glycoproteins that help platelets adhere together are not functional or present, it can also lead to bleeding problems. The platelets are there, but they can’t do anything.
◦ You can have problems with the function or the # of platelets.
integrity platelets coagulation vascular number von willebrand
What are bleeding disorders?
• You can also have ____ factor problems in that the coagulation factors can be deficient (have an inadequate #)
• You can have problems with coagulation inhibitors (____) which help prevent excessive clotting there.
◦ The antibodies (Protein C, Protein S) go within the bloodstream to prevent excessive clotting. But if they’re hyperactive, where you have these factor inhibitors, when they’re too abundant, you have too much ____.
◦ In sum–> Its goal is to prevent clotting. But if they’re too abundant, it leads to excessive bleeding.
• Even though the Fibrinolysis Phase is to breakdown your clots, if it’s happening too ____, it can lead to bleeding.
coagulation
protein C, protein S
bleeding
rapidly
Lab studies - bleeding disorders
Lab studies - bleeding disorders
Platelet count: ____ cellsmm3
Normal Prothrombin time (PT): ____ seconds
Partial thromboplastin time (PTT): ____ seconds
Thrombin time (TT): ____ seconds
PFA 100
Bleeding time- no ____ in use
• Complete Blood Count is always a standard to rule out a bleeding disorder.
◦ It will have red blood cell, white blood cell, platelets, and your differentials for your red blood
cells and white blood cells.
◦ The ____ are what we’re specifically looking for here (for bleeding disorders)
‣ The normal platelet count is important to know. When you know this figure, you’ll know if there’s a problem and you’ll be able to anticipate problems in your dental chair.
‣ Regular platelet count: 150,000-400,000
◦ Sometimes when you have a condition called ____, where you have too much
red blood cells, you’re also concerned with the red blood cell count.
150,000-400,000 11-13.5 25-35 12-14 longer
platelets
polycythemia vera
Lab studies - bleeding disorders
◦ Ask for normal Prothrombin Time (PT). This is for ____ pathway. [reads normal]
◦ Activated Partial Thromboplastin time (aPPT) is for ____ pathway [reads normal]
◦ Thrombin Time (TT) tells you from when ____ is activated to when Fibrin is formed.
Sometimes they will request TT.
◦ In the past, they used Bleeding Time, but that didn’t tell you much about the function of your
platelets. No longer in use.
◦ These days, they use more of the ____.
◦ In addition to your CBC, they also do a ____ Smear. This tells you about the morphology
of your platelets. Are they too big or too small?
extrinsic intrinsic factor 10 platelet function analyzer 100 peripheral
Concerns with Platelet count
____ cells/mm3 – mild bleeding after trauma
____ cells/mm3– moderate bleeding after trauma
50,000-100,000
20,000-50,000
20,000
2
Bleeding disorders
____
____/congenital
acquired
inherited
Acquired bleeding disorder \_\_\_\_ Drugs \_\_\_\_ Chemotherapy
• Medications: patients with bleeding disorders are on these, some have to do with clotting factors ◦ There are a lot of anti-platelet medications
‣ Plavix: being used in patients with ____ or patients at risk of ____
◦ Sometimes anti-____ medications
• Radiation usually would lead to ____ of the precursors that will form platelets in the bone marrow.
◦ Patients that receive radiation therapy are at risk for ____. This could lead to an aquired bleeding disorder because of deficient platelets.
• Same thing in ____. It’s killing the cancer cells in patients with Leukemia and things like that. ◦ In killing the cancer cells, the precursor cells are sometimes targeted and that also leads to
deficiency in platelets (thrombocytopenia).
disease
radiation
atrial fibrillation DVT coagulation depletion chemotherapy
Acquired bleeding disorder
Disorders affecting ____ phase
Disorders affecting ____ phase
Disorders affecting ____ phase
vascular
platelet
coagulation
Acquired bleeding disorders
Vascular defects:
____ vessel malformation
Acquired ____ tissue (CT) disorders
structural
connective
Vascular defects- acquired CT disorders
Small vessel vasculitis
Any conditions that cause ____ of small vessels- arterioles, venules and capillaries
Arteriovenous Malformation ____ most common
____ > Female
inflammation
brain AVM
male
1
arteriovenous malformation (AVM)
uterine
brain
blood vessels
Acquired vascular defects - acquired CT disorders
- SCURVY
____ def > weakened ____ fibers > defective ____ supportive tissue > capillary ____
• Scurvy is an acquired CT disorder. It leads to fragility of your blood vessel wall because your CT is not intact. Scurvy can weaken your ____ and lead to capillary fragility.
vit. C collagen perivascular fragility collagen fibrils
Acquired vascular defects - acquired CT disorders
- STEROID USE (long term)
thinning of ____ tissue > bleeding after ____ trauma
• If a patient is also on long-term steroid use, if they just bump their hands, they bleed. Their CT becomes thinner the longer they’re on steroids. So they have a high risk of bleeding after minor trauma.
connective
minor
Vascular defects- acquired CT disorders
- SERUM SICKNESS
____ deposits into vessel walls > ____ (skin hemorrhage - 4-10mm)
Serum-sickness like reactions:
drug-induced- ____, hydralazine, ____, diuretics ____ induced
- Serum sickness is a kind of reaction to horse serum which is used in the treatment of things like ____ and Diptheria. It’s an ____ reaction to horse serum causing fever, rashes, and arthralgia. It makes the CT of the blood vessel more fragile and can lead to bleeding under the skin (purpura).
- Even though horse serum is what causes Serum Sickness, some medications give a similiar presentation of the arthritis, rashes and fever. They are termed Serum-sickness like reactions. Some of these medications include ____ (??)(which is an antibiotic), penicillins, ____ and diuretics.
immune complex purpura penicillin sulphonamide hepatitis
scarlet fever
allergic
cephalaco
sulfonamides
Acquired platelet disorder - Platelet function disorder
Platelets- form ____ for the adherence of clotting factors
Involved in clotting cascade by release of platelet ____
Serve as constituents of ____
Serve as constituents of ____ converting complexes
- The platelets and coagulation factors really interact in forming your temporary clot. The platelets also interact in the presence of platelet ____ to help stabilize your Fibrin Mesh.
- You could have problems with the platelet number. or function of the platelets.
scaffold factor 3 factor X prothrombin factor 3
Acquired Platelet function disorder (PFD)
Drugs- ____, β- lactam antibiotics, ____ channel blockers, Aspirin
Diseases- ____ dx, liver failure, ____
Foods/supplements- ____, garlic, ____, omega-3 fatty acids
• Ca channel blockers: things like Nifedipine, Verapamil can impair the normal functioning of your
platelets
• Certain food supplements like ____ fatty acids or garlic and ginger. You might have heard that if you’re on Warfarin you have to avoid garlic and ginger. In patients, garlic and ginger also cause impairment of platelets (they are natural ____, basically).
◦ So in patients that already have a bleeding problem, this can impair their platelet function further
NSAIDS Ca kidney tumeric omega-3 blood thinners
Acquired coagulation disorder- DIC
Clinical presentation:
Acute DIC
Accelerated ____
Bleeding from small wounds ____
Spontaneous bleeding
Chronic DIC: e.g. ____, SLE ____ (blood clots are formed)
• DIC: disseminated intravascular coagulopathy
◦ Can occur after ____ (usually viral), surgery or after snake bites
◦ It can go 2 ways. In the acute form, you’re having too much breakdown of your ____ that is
formed. Normally, ____ helps you break down clots at the end of hemostasis. But this is happening too rapidly and this causes bleeding or hemorrhage.
◦ When you have it in the chronic form, it results in ____ clotting.
◦ DIC is when you’re concerned about ____. You can see bleeding under the skin (purpura).
fibrinolysis
purpura
cancers
thrombosis
fibrin
fibronolysis
excessive
bleeding
Management of DIC
____ ( if bleeding)
FFP
____ ( if thrombosis)
Platelet replacement, clotting factor replacement
Avoid use of plasmin and plasmin product inhibitors e.g. ____
- If a patient has acute DIC, you want to give them Cryoprecipitate. It’s a product of plasma that contains ____ and ____ factors. The patient is bleeding, so you want to ensure that you’re having clot formation. You can also give them ____.
- If a patient has chronic DIC, you want to give ____. It’s an anti-thrombin inhibitor. It works on thrombin to make sure you’re having less clotting occuring.
cryoprecipitate
heparin
tranexamic acid
fibrinogen
clotting
fresh frozen plasma (FFP)
heparin
ACQUIRED Fibrinolytic disorder
- Hyperfibrinolysis
- Too much ____
– early breakdown of clots - ____ disease
- severe trauma
- PT, aPTT or TT – not ____ in diagnosis
- For your acquired fibrinolytic disorders, you have too much fibrinolysis or too rapid breakdown of your clots which will lead to bleeding also.
- If your plasminogen is in excess, it causes too much ____ of clots. You can also see this associated with severe trauma or patients with liver disease.
- With fibrinolysis, its the dissolution of the clot. Even though the patient is bleeding, the PT, aPTT, or TT do NOT play a role in diagnosis of hyperfibrinolytic problems.
plasminogen
liver
helpful
breakdown
Acquired bleeding disorders -Liver disease
Most coagulation factors are produced in the ____.
Liver disease if significant can cause severe bleeding
Also risk of ____ from platelet sequestration in spleen
Heavy ____ -causes liver damage
• Since the spleen sequesters the platelets, so if it is hyper-functioning the platelets will be broken down and lead to more of a bleeding risk
liver
thrombocytopenia
alcoholism
Other conditions -acquired bleeding disorders
Chronic leukemia –\_\_\_\_ phase disorder Vit.K Malabsorption syndrome/ long term \_\_\_\_ therapy (intestinal bacteria producing Vit K maybe affected) End stage renal disease \_\_\_\_ Infections -?\_\_\_\_ –Hemorrhagic fevers
platelet
antibiotic
hypersplenism
viral
Indirect thrombin inhibitors - Heparin
Inhibits ____ and thrombin
Given by ____ infusions
Need to monitor ____
Half life is ____hours(standard heparin)
LMWH- ↑ activity on Factor ____ e.g. enoxaparin (lovenox)
v ____ half-life (2-4hrs) vSubcute. ____
• LMWH - low molecular weight heparin
◦ Remember this: regular heparin is given through IV and LMWH is subcutaneous*
◦ LMWH is preferred because…
‣ It has double the half life of normal heparin
‣ You don’t have to monitor your aPTT as regularly as you would with normal heparin
factor Xa IV aPTT 1-2 Xa longer administration
Direct thrombin inhibitor
Dabigatran (Pradaxa) Orally administered
Used to prevent ____ in patients with
____
stroke
a. fib
Factor Xa inhibitor
____ (Xarelto)
Apixaban (Eliquis)
Both ____ administered
rivaroxaban
orally
Vit. K dependent coagulation protein inhibitor
Warfarin (Coumarin)
____
competitively inhibits ____ (enzyme for Vit K activation)
Inhibits factors ____, VII,____,X ____ administered
Monitored with ____
anticoagulant vitamin K epoxide reductase complex 1 prothrombin (II) IX orally PT/INR
Inherited bleeding disorders
Not as common as ____ bleeding disorders
Epidemiology: 10-20 in 2000 patients
acquired
Congenital/inherited bleeding disorders
Alteration of vascular wall
Hereditary hemorrhagic telangiectasia
- bleeding defect > problem w wall ____ > ____
- most ____ defect
integrity
petechiae
common
Congenital/Inherited – Platelet disorder
____ dx
Bernard- Soulier
Glanzmann thrombasthenia
____ syndrome
____ anomaly
____
- these three > abnormal platelets larger in size and fewer in number
von willebrand
gray platelet
may-hegglin
hereditary thrombocytopenia
Congenital/inherited bleeding disorders
Disorders of coagulation
Hemophilia A ( factor ____ def) Hemophilia B(factor ____ def)
Primary congenital deficiencies of fibrinolytic inhibitors
____ [A2AP]
____ [PAI-1]
VIII
IX
alpha-2-antiplasmin
plasminogen activator inhibitor-1
Vascular defect- Hereditary hemorrhagic telangiectasia
\_\_\_\_ 1:8000to 1:50000 Petechiae \_\_\_\_ have inherent mechanical fragility Noted on \_\_\_\_ membranes Tx: \_\_\_\_, surgery, \_\_\_\_ replacement, thalidomide
rare blood vessels skin and mucous laser hormonal
Congenital connective tissue disorders associated with bleeding \_\_\_\_ disease Osteogenesis imperfect \_\_\_\_ elasticum Marfan syndrome
ehlers-danlos
pseudoxanthoma
Von Willebrand disease- platelet function disorder
Most \_\_\_\_ inherited bleeding disorder Affects 1% of US population \_\_\_\_ trait –mild to moderate clinical bleeding type 1 (70-80%cases) type 2A(15-20%cases) \_\_\_\_ form (Type 3) Other forms- rare
common
autosomal dominant
autosomal recessive
Von Willebrand disease– signs and symptoms
Mild forms-____/cutaneous bleeding
Severe forms: ____, dissecting intramuscular ____
mucosal
hemarthrosis
hematoma
Diagnosis of Von Willibrand’s dx Prolonged \_\_\_\_ (\_\_\_\_ is normal) \_\_\_\_ or low platelet count von Willebrand specific: \_\_\_\_ cofactor activity - – vWF to GP 1b \_\_\_\_ induced platelet aggregation. vWF \_\_\_\_ Specific factor \_\_\_\_ assay
aPTT PT normal ristocetin ristocetin immunoassay VIII
Treatment
Desmopressin-risk of thrombosis in ____ patients with ____
____ acid
____ (prepared from plasma)- contains ____, factor VIII, ____ fibrinogen, factor XIII
Factor ____ replacement that retainsvWF
elderkly
CVD
aminocaproic
cryoprecipitate
vWF
fibronectin
VIII
Bernard- Soulier disease
Caused by lack of ____ which prevents binding of vWF to platelets
platelets ____ and defective
Clinical features- skin ____, epistaxis,
irregular heavy menstrual bleeding
Tx: platelet ____, desmopressin, Factor ____
glycoprotein Ib large bleeding transfusion VIIa
Glanzmann thrombasthenia
Disorder of platelet aggregation
Abnormality of platelet membrane complex ____ (fibrinogen receptor)
____ trait
Platelets adhere to ____ (via
vWF) but cannot bind to ____
Higher frequency with consanguinity e.g.
____, Iranians etc
glycoprotein IIb/IIIa autosomal recessive subendothelium fibrinogen indians
Gray platelet syndrome
Very ____
Abnormal platelet disorder – ____ and ____ # of platelet
____ gene disrupt the normal production of alpha-granules
____ - fibrous scar in bone marrow
rare large decreased NBEAL2 myelofibrosis
Coagulation disorder-
Hemophilia A
Factor \_\_\_\_ deficiency Most \_\_\_\_ inherited coagulation bleeding disorder 1 in every 5000 male births \_\_\_\_ trait Clinical manifestation- \_\_\_\_, hematoma, \_\_\_\_
VIII common x-linked recessive ecchymosis hemarthrosis
Hemophilia A
Lab findings, prolonged ____, normal PT and ____ count.
Management: avoid ____,
aPTT
platelet
NSAIDS
Coagulation disorder-
Hemophilia B
Deficient factor ____
____ trait
IX
X-linked recessive
Oral manifestations of bleeding disorders
\_\_\_\_ in oral mucosa Spontaneous gingival bleeding \_\_\_\_ Jaundice \_\_\_\_ TMJ Hemathrosis –\_\_\_\_ factor disorder
petechiae
ecchymosis
pallor
coagulation
Oral manifestations of bleeding disorders
Enlarged ____ glands- ____ liver dx (usually alcoholism)
Leukemia-generalized gingival ____ & bleeding
Neoplasm-osseous lesions, ____, oral ulcers, loosening of teeth, ____ (burning,numbnessinlip)
parotid chronic enlargement tumors paresthesia
Signsand symptomsof bleeding disorders
Vascular phase- ____ and ____ membrane/skin bleeding
Platelet phase – ____, ____
Coagulation phase- ____,
hemathrosis, ____,
petechiae
mucous
petechiae
ecchymosis
ecchymosis
hematoma
Platelet disorder
Bleeding after cuts and sutures: ____
Bleeding post surgery/trauma: ____
Coagulation disorder
Bleeding after cuts and sutures: ____
Bleeding post surgery/trauma: ____
yes
immediate
no
delayed
Dental management
Thrombocytopenia -
30,000
80,000 to 100,000
Dental mangt (contd)
____ dental care important in hemophiliacs
Avoid ____ block, IM injections, injection into ____, lingual infiltration
____ (5%),orally or before and after extraction
preventive
IAN
FOM
tranxemic acid
Dental management (contd)
Avoid ____ in patients taking warfarin
INR should be between ____ in at risk pt groups (taking warfarin)
Avoid ____, broad spectrum antibiotics in this group of pts
Follow up within ____ hrs after surgical procedures
aspirin
2-3.5
NSAIDS
24-48
