4. Bleeding Disorders Flashcards by J L

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

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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

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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

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Hemostasis

Primary phase
􏰓____ phase
􏰓____ phase

Secondary phase
􏰓____ phase

􏰓____ phase- where clot is dissolved

vascular
platelet
coagulation
fibronlytic

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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

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• 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

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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

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• 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]

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Vitamin k dependent clotting factors
􏰓Factor \_\_\_\_ 
􏰓Factor \_\_\_\_
􏰓Factor \_\_\_\_
􏰓Factor \_\_\_\_

II
VII
IX
X

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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

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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

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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

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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

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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

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Bleeding disorders
􏰓 ____
􏰓 ____/congenital

acquired

inherited

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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

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Acquired bleeding disorder
􏰓Disorders affecting ____ phase
􏰓Disorders affecting ____ phase
􏰓Disorders affecting ____ phase

vascular
platelet
coagulation

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Acquired bleeding disorders
􏰓Vascular defects:
􏰔____ vessel malformation
􏰔Acquired ____ tissue (CT) disorders

structural

connective

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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

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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

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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

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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

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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