©The Maxillofacial Center for Diagnostics & Research

The Maxillofacial Center, 165 Scott Avenue, Suite 100, Morgantown, WV 26508 USA
Phone: 304-292-4429   Fax: 304-291-5149    Email: MFC@aol.com

Jerry E. Bouquot, DDS, MSD: Director of Research, The Maxillofacial Center for Diagnostics & Research, Morgantown, West Virginia; Former Chairman, Department of Oral & Maxillofacial Pathology, West Virginia University School of Dentistry, Morgantown, West Virginia

Michael G. LaMarche, DDS: Private practice, Lake Stevens, Washington; Clinical Investigator, The Maxillofacial Center for Diagnostics & Research, Morgantown, West Virginia

Statement of problem. Previous investigators have identified focal areas of alveolar tenderness, elevated mucosal temperature, radiographic abnormality, and increased radioisotope uptake or "hot spots" within the quadrant of pain in most patients with chronic, idiopathic facial pain (phantom pain, atypical facial neuralgia, atypical facial pain, etc.).

Purpose. The present retrospective investigation radiographically and microscopically evaluated intramedullary bone in a certain subset of patients with histories of endodontics, extraction and fixed partial denture (FPD) placement in an area of "idiopathic" pain.

Material and methods. Patients from 12 states were identified through tissue samples, histories and radiographs submitted to a national biopsy service. Imaging tests, coagulation tests and microscopic features were reviewed.

Results. Of 38 consecutive idiopathic facial pain patients, 32 were female. Approximately 90% of subpontic bone demonstrated either ischemic osteonecrosis (68%), chronic osteomyelitis (21%) or a combination (11%). More than 84% of the patients had abnormal radiographic changes in subpontic bone, and five of nine (56%) patients who underwent radioisotope bone scan revealed hot spots in the region. Of the 14 patients who had laboratory testing for coagulation disorders, 71% were positive for thrombophilia, hypofibrinolysis, or both (normal: 2-7%). Ten pain-free patients with abnormal subpontic bone on radiographs were also reviewed.

Conclusions. Intraosseous ischemia and chronic inflammation were suggested as an pathoetiologic mechanism for at least some patients with atypical facial pain. These conditions were also offered as an explanation for poor healing of extraction sockets and positive radioisotope scans.

This study has shown that painful and radiographically abnormal bone under fixed partial denture pontics typically demonstrates diseased cancellous bone and marrow. Usually diagnosed microscopically as ischemic osteonecrosis or chronic osteomyelitis, this diseased bone is capable of producing varied, often severe, pain, and is also capable of interfering with proper alveolus healing and remodeling after extraction. Most affected patients have a previously undiagnosed, underlying clotting defect.

Introduction to the Problem

When a dentist cannot identify a dental or temporomandibular origin for chronic facial or jaw pain, the most frequent assumption for the cause of discomfort has been a disorder of the trigeminal nerve. Diagnostic terms such as neuralgia, causalgia, phantom pain, deafferentation, hyperalgesia and anesthesia dolores are applied, depending on the patient’s symptoms.^1-3 This is typically the termination of the diagnostic work-up, except for CT or MRI scans to exclude tumors or vascular abnormalities of the brain. Many patients then drift from one health professional to another in an understandable attempt to eliminate pain. Additional health care professionals reconfirm the initial neuralgic diagnosis and concentrate on administration of an effective medication or other pain-control therapy, or discovering the psychological origin for the patient’s "self-inflicted" pain.

However, there is another class of pain-producing conditions that require no nerve damage to explain chronic "idiopathic" pain. These conditions are related to compromised blood flow through bone marrow or low-grade inflammatory changes of medullary tissues (Table 1). Many of these diseases create no swelling or erythema of overlying skin or mucosa, no alteration in routine laboratory values, and minimal or no aberrant radiographic images of an affected area. This article examined one of these maladies, ischemic osteonecrosis, a relatively common disease of the human skeleton, responsible for approximately 20% of all hip replacements in the United States.^4-11 The disease is also known by a variety of other names: aseptic osteomyelitis, avascular necrosis, transient ischemic osteoporosis, transient ischemic arthritis, medullary engorgement-pain syndrome, bone marrow edema syndrome, and bone compartment disease.^4-11

Almost every human bone can be affected by ischemic osteonecrosis. This includes such strange locations as the bony wall of the ear canal, where it has been called necrotizing (malignant) otitis externa. It seems remarkable that a disease that has been known for generations has only recently been recognized as occurring within the marrow spaces of the jaws.^12-17 Perhaps this has occurred because jawbone examples are usually among the less severe cases (relative to marrow damage, not to pain). This disease is also notorious for its lack of obvious radiographic changes until extensive destruction.^8,18,19 Radiographic and other imaging changes are commonly so subtle that radiologists have created a unique Stage 0 classification for those cases which are completely negative to all known forms of imaging technology (Table 2).^7,8,10 The present investigators have been unable to find another radiographic entity for which a Stage 0 classification was included as part of a routine diagnostic protocol.

This disease, once called coronary disease of bone because of its ischemic and infarctive phenomena, usually affects the long bones, especially the head of the femur.⁸ Trauma and infection are well-established "causes" or triggering events for osteonecrosis. It seems ironic that the jawbones, the most traumatized bones of the skeleton and the bones most likely to become infected, have until recently never been reported with osteonecrosis except in individuals irradiated for cancer (osteoradionecrosis).^15,20,21

Friedman²² recently reported that 15 of 18 patients with chronic idiopathic facial pain (atypical facial pain) had localized areas of alveolar tenderness in the painful quadrant. Seventeen of the 18 also had areas of elevated mucosal temperature in the painful quadrant. Denucci et al²³ expanded the research by evaluation of a similar group of patients with SPECT (Single Proton Emission Computed Tomography) scans designed to identify medullary inflammatory or osteonecrotic disease. A remarkable 75% of the patients had localized "hot spots" of increased isotope uptake within the quadrant of pain. Areas of reactive periodontitis and periapical pathoses were excluded by study design. These results suggested that intraosseous inflammation or osteonecrosis were associated with chronic idiopathic facial pain, but neither study included bone biopsies in its protocol.

This investigation was designed to proceed with the next logical step. The study evaluated microscopic features of the alveolar bone of patients with idiopathic facial pain and areas of tenderness/pain, abnormal radioisotope uptake or abnormal radiographic appearance in the quadrant of pain. Because of certain documented histories or scenarios, it was elected to specifically examine areas of previous extraction and prosthetic replacement in the same quadrant as the facial or jaw pain. Subpontic marrow biopsy samples were specifically assessed for various patterns of osteomyelitis and osteonecrosis. Because a large proportion of patients with osteonecrosis are pain free, a certain number of patients without histories of pain were also evaluated. These had routine FPDs but demonstrated radiographic evidence of poor healing of a subpontic extraction site.

A common scenario in the practice of general or prosthetic dentistry involves the patient who describes a chronic, localized "toothache" without an obvious etiology. After some empirical dental procedures, such as occlusal adjustment, replacement of restorations and then endodontic treatment with apicoectomy, the offending tooth is usually extracted.

Two problems may then result. Firstly (Case 1 scenario), the pain may remain, at which point neurologic diagnoses are typically applied.²⁴ Secondly (Case 2 scenario), the pain may disappear for months or years, only to re-emerge when the adjacent teeth are prepared for a FPD and the dentist is accused of causing the pain. A frustrating subset of this group has no pain prior to dental treatment, and the litigious nature of this predicament is obvious.²⁵ All pain-affected patients in this study followed one of these scenarios.

Methods & Materials

Consecutive intramedullary biopsy samples were submitted to the national biopsy service, Head & Neck Diagnostics of America (Morgantown, West Virginia). The biopsies included radiographs that allowed the identification of the sample as subpontic alveolar bone. Blind biopsies of subpontic bone were not performed prospectively, for ethical reason, during this study. The analysis included only retrospective cases and undoubtedly suffered from sample-collection biases of all clinicopathologic reports which use databases from surgical pathology services.²⁶ In other words, the sample did not represent a particular population, only patients biopsied because of idiopathic jaw pain or radiographic abnormalities, according to attending surgeons who submitted specimens.

Forty-nine patients (41 women, 8 men) were identified in the archives of Head & Neck Diagnostics, representing biopsy submissions from 21 dentists or oral surgeons in 12 U.S. states. When appropriate information was unavailable on the surgical pathology request form received with each tissue sample, the professional was called to confirm the presence or absence of pain at the biopsy site, and to confirm that there was no surgery at the site for at least a year prior to biopsy. No patient demonstrated periodontitis or mucosal erythema at the site at the time of biopsy. All patients with pain had experienced temporary but complete or almost complete pain reduction with local anesthesia, with the anesthesia/hyperesthesia test of Ratner-McMahon,^27-29 or the Wrobleski periosteal microanesthesia test. The Wrobleski test consisted of the injection of a small amount of local anesthesia, without vasoconstrictor, in the periosteum of the facial surface of alveolar bone directly over the area of suspected pain induction.

99Technitium MDP bone scans or SPECT scans are radioisotope imaging tests widely used for osteonecrosis.^4-10,15 Pre-operative scans were available for nine of the identified pain cases. Recent research has also convincingly identified a variety of hypofibrinolysis and thrombophilia factors in the great majority of patients with osteonecrosis of the hip, knee and jaws (Table 3).^30-35 Laboratory results relating to coagulation function were available for fourteen patients in the pain cohort. None of the patients had been formally evaluated for elevated mucosal temperature, with the technique of Friedman.²²

Additionally, 11 consecutive biopsy samples were identified in patients without histories of pain in the area, but with radiographic abnormalities of alveolar bone beneath a pontic. This patient cohort excluded patients who had extractions or other surgical procedures in the subpontic area during the previous year.

Histopathologic criteria for osteonecrosis and osteomyelitis in this investigation were selected from standard orthopedic and rheumatologic texts and contemporary reports.^{4-12,15,36,37} All diagnoses were confirmed by an oral and maxillofacial pathologist with extensive experience in inflammatory bone diseases and a Bone Pathology Fellowship at Mayo Clinic, Rochester, Minnesota.

Results

Thirty-eight pain patients were identified and consisted of 32 women and six men. Of these, thirty one patients had histories of spontaneous, continuous, worsening pain not obviously associated with, or alleviated by, dental treatment. They followed the Case 1 scenario. The additional seven patients included those with pain initiated or recurring in the affected site within days or weeks of abutment preparation or FPD placement, i.e. they followed the Case 2 scenario. Of the 11 patients without pain histories, nine were women and two were men. All had innocuous tooth preparations and placement of FPDs, but exhibited radiographic abnormalities in subpontic bone.

The average age of patients at biopsy was 48 years (range: 24-76), but was slightly less for the group of patients with pain than without facial pain (Table 4). Of the 38 pain patients, investigated subpontic bone included 23 cases from molar sites, nine from premolar and six from lateral incisor areas, with even distribution between the maxilla and mandible, except incisor areas, which were all in the maxillary arch. Patients without pain involved mainly molar regions, with the exception of two cases from the maxillary incisor region.

Approximately 75% of the patients, including those without pain, demonstrated radiographically visible vertical remnants of lamina dura within subpontic bone (Table 4). More than a third of patients displayed a relatively complete, albeit sometimes faint, outline of the former tooth socket, while an additional 41% showed only ragged, often zigzagged vertical remnants of the dura (laminar rain, laminar lightning), with apparent remodeling or healing of the apical portion of the socket (Figs. 1-5). Two residual sockets were more sclerotic than surrounding bone (socket sclerosis³⁸) (Fig. 6), but the others were slightly radiolucent compared to normal bone.

Additionally, almost 60% of patients demonstrated irregular, ill-defined radiolucencies within subpontic bone, often with a triangular shape with the base of the triangle parallel to the crest of the ridge (Fig. 7). These varied from 3 mm. to 10 mm. in size and were often identified in radiographs lacking a substantial residual lamina dura. Some radiolucencies had scalloped borders, but without sclerosis of the border. The radiolucency typically extended outside the lamina dura when a residual socket was present.

Three patients demonstrated well-demarcated radiolucencies of the affected areas with scalloped borders and small, irregular areas of radiopacity in the subpontic bone (Fig. 8). These were similar to chronic sclerosing osteomyelitis. One patient exhibited subpontic osseous hyperplasia of the crest of the ridge (Fig. 8). Six patients demonstrated no radiographic abnormalities whatsoever in the area of localized pain.

Of the nine pain patients who had ⁹⁹technitium bone scans (n=6) or SPECT scans (n=3), five showed areas of increased radioisotope uptake or "hot spots" in the subpontic bone (Fig. 9). This was less than the 70-80% previously reported for maxillofacial osteonecrosis/osteomyelitis patients, but of course the sample was rather small and was not representative.^15,23,39 Two of the five positive cases were among those that revealed no abnormalities on the routine radiographs.

Of the 14 pain patients for whom laboratory values were recorded, ten (71%) demonstrated hereditary or acquired coagulopathies; all in patients with microscopic evidence of ischemia or infarction of marrow (Table IV). This was similar to the proportion found in previous, larger cohorts of patients with osteonecrosis of various bones (65-87%), is more than the 20-50% found in patients with deep venous thrombosis of soft tissues, and is considerably more than the 2-7% found in the normal population (Table 3).^30-35

Approximately 90% of subpontic bone demonstrated ischemic osteonecrosis, chronic osteomyelitis, or both (Table 4). Representative tissue is presented in Figs. 10-12; normal fatty marrow is demonstrated in Fig. 13 for comparison. Pain patients were more likely (79%) to suffer from marrow ischemia and infarction, while non-pain patients were more likely (73%) to have osteomyelitis. Of the 34 pain patients with osteonecrosis, four also showed evidence of chronic osteomyelitis. Conversely, of the 12 pain patients with osteomyelitis, four were combined osteomyelitis and osteonecrosis.

Acute infection was not demonstrated in any specimen and all tissue from patients with positive radioisotope scans was positive for bone disease: six osteonecrosis, one chronic osteomyelitis and two with a combination of both entities. This lack of false positives is in accordance with literature on bone scanning of osteonecrosis.⁴⁰ One tissue sample from a patient with known hypofibrinolysis, and two samples from patients without laboratory data available, also demonstrated fibrin/platelet aggregates in marrow tissues; one revealed these aggregates within dilated veins (Fig. 14).

Almost 11% of all patients demonstrated microscopically normal bone and bone marrow. These patients may have truly had normal marrow, or this may have represented tissue sampling errors or tissue from less involved patients with relatively complete healing of the bone by the time of biopsy. These five cases demonstrated radiographic abnormalities, but only three were tender to palpation; two were discovered in patients without histories of pain; one fit criteria for hematopoietic marrow defect.

Discussion

The purpose of this investigation was to evaluate subpontic bone in sites of FPD placement which also were associated with pain or radiographic abnormality. The results were certainly intriguing. Osteonecrosis or nonsuppurative osteomyelitis was discovered in alveolar bone of almost 90% of patients with chronic idiopathic facial pain. This offered an explanation for localized alveolar tenderness, elevated mucosal temperatures and positive bone scans reported by Friedman²² and Denucci et al²³ in idiopathic facial pain patients. It served as a clear warning that bone-related pain may explain idiopathic pain that began as toothache-like pain and evolved into phantom pain or facial neuralgia.^24,39

Persistent remnants of lamina dura after extraction may be more than a simple variation of normal radiographic anatomy. This study suggests that it is more reasonable to consider laminar rain as a sign of underlying inflammatory or physiologic processes which were preventing proper remodeling of bone. Bone is a dynamic tissue in constant flux and there was no physiologic reason for post-extraction alveolar bone not to remodel to accommodate the new lack of tooth-related stresses.^41,42

Under ischemic conditions, intraosseous fibrous "scar" tissue (marrow fibrosis, reticular fatty degeneration, myelofibrosis) is created rather than new bone, because osteoblasts and osteoclasts require abundant nutrition and oxygen to perform physiologic functions, while fibroblasts do not.⁴³ Fibrosis of marrow is a profound alteration. Fibers in bone marrow are usually small in size and numbers, and almost invisible on stained microscopic slides. Presumably, laminar rain represented this fibroplasia phenomenon, with the extraction socket becoming permanently filled with fibers rather than with new bone.

Laminar rain did not allow a formal diagnosis, it served merely as a "red flag" that something may be wrong with the local bone. Cancellous bone does not usually exhibit obvious radiolucent destruction until disease is in late stages (Stages 3 and 4 in long bones), so radiographic signs of poor healing in earlier stages is significant.⁴⁰

A lesson can also be derived from what is not observed. Dramatic damage to cancellous bone is possible without radiographic evidence of change. This occurs especially in the ends of long bones and particularily with lesions, such as osteonecrosis and osteomyelitis, which do not have a sharp demarcation from surrounding bone.⁴⁴ Similar evidence has been available for alveolar bone of the jaws,^45-47 but most dentists tend to forget this. A lack of radiographic changes does not necessarily indicate that bone contains no pathology. False negatives can occur, as they do in other tests.

What is osteonecrosis?

Ischemic osteonecrosis is not a disease in the usual sense but is the result of a wide variety of local and systemic disorders that eventually lead to ischemia and infarction of the marrow and bone (Table 5). For example, when a jawbone is irradiated the blood vessels are damaged, become entombed by fibrous tissue and lead to a chronically poor blood flow (after initial hyperemia) with the often painful condition previously mentioned as osteoradionecrosis. The medullary blood flow is similarly compromised in corticosteroid-induced osteonecrosis, not by fibrosis but by endothelial injury and outflow veins partially collapsed by enlarged adipocytes.^7,10,36

A more common mechanism of compromised marrow blood flow has been blockage of the vessels by thrombi. Multiple bone infarctions, for example, have been a major medical problem of patients with sickle cell anemia.^11,15 Rigid erythrocytes become blocked within the smaller vessels of the marrow and the resulting localized infarction is often extremely painful. Other causes of intramedullary infarction have been less obvious. A substantial breakthrough was achieved, however, by Glueck, et al^30-35 who reported that a majority (65-87%) of osteonecrosis patients, including those with jawbone involvement, had major hereditary or acquired clotting disorders that had not been previously diagnosed or even suspected (Table 3).

The alveolar bone and the mandibular condyles appear most susceptible to this disease, usually diagnosed under the respective terms NICO (neuralgia-inducing cavitational osteonecrosis) and avascular condylar necrosis.^15,48 Alveolar lesions are most likely misdiagnosed as facial neuralgias, as NICO diagnostic terminology implies. Perhaps this is because the jawbones are the only bones of the human skeleton to contain large sensory nerves. Therefore, the level of pain is greater or the pain is different from that produced by disease in other bones. This problem is compounded by the high proportion of false negatives on routine radiographic evaluation, and by low levels of diagnostic suspicion demonstrated by health care professionals.

It has been suggested that a proportion of facial neuralgia patients have persistent pain from trigeminal nerve damage at some distance from the brain, including nerves within inflamed jawbones.^49,50 The pain could be created by damage to peripheral nerves (neuritis, deafferentation, demyelination), and occasional NICO patients have certainly demonstrated degeneration of myelin sheathing of intraosseous nerves.¹⁶ Some have even demonstrated anti-myelin antibody levels consistent with chronic exposure of the immune system to damaged myelin.^51,52 Ischemic osteonecrosis appeared a significant contributor to this process from this and previous studies.

However, pain, recurrence and multifocal involvement are hallmarks of osteonecrosis, regardless of the exact cause, and nerve damage is not necessary to produce the pain. Osteonecrotic pain has been shown to typically result from increased intramedullary pressure, which can be five times greater than normal and is routinely twice that of normal bone.^7,36,53,54 This has generally resulted from poor outflow from the bone and is unique to ischemic osteonecrosis. Certain authorities have advocated diagnostic injection of saline in marrow of painful bones lacking obvious radiographic changes. The pain increases in osteonecrosis patients but not in others.³⁶ Intraosseous stasis and hypertension, first noted in osteoarthritis, is especially associated with a deep, aching pain at rest.^53-55

The pain of osteonecrosis may also be due to venous distension, and the pain stimulus may originate in the vein wall.⁵³ Additionally, it may be due to diminished blood flow from intravascular microthrombi, as recent clinical research has demonstrated major pain reduction in jawbone osteonecrosis patients with anticoagulants.⁵⁶ NO-liberating organic nitrates, such as nitroglycerin, have been effective in controlling pain in localized ischemic conditions of other parts of the body, such as anal fissures.⁵⁷ However, these medications have not been administered for NICO patients.

Other causes of deep bone pain are associated with osteonecrosis. Infarction resulting from the complete, abrupt blockage of marrow blood vessels creates an immediate and sharp pain. Toxins and inflammatory mediators, such as prostaglandin E₂ and other cytokines routinely released from necrotic tissues and local inflammatory responses, may result in a variety of different pain symptomatologies over an extended period.^58-60 Additionally, infection of cancellous bone further compromises local blood flow and enhances coagulation. New microinfarctions can occur in adjacent marrow, only to repeat the entire process again.

Case 1 scenario, previously mentioned, is not difficult to explain by extrapolating the results of research for other bones. Steadily increasing intramedullary hypertension from poor outflow results in painful claudication and possible tissue death, similar to pulpal events in an injured tooth. Small infarctions (microinfarctions) elicit additional pain and a corresponding inflammatory response. Inflammatory mediators further diminish local blood flow, compounding the problem and perhaps establishment of a perpetually spiraling cycle of increasing disease and pain.

Case 2 scenario, with pain beginning or recurring with tooth preparation or prosthetic placement, is more difficult to understand. The mild pulpal inflammation natural to the tooth reduction may carry inflammatory mediators into apical bone, but this appears unlikely and, besides, alveolar osteonecrosis seldom occurs at the exact apex of a tooth. It is a disease of paradental or interdental bone, not periapical pathosis.

There is a more logical explanation for Case 2 scenario. Almost all local anesthesia used in dentistry today includes a potent vasoconstrictor. In a person with seriously compromised intraosseous vascular flow, the diminished blood flow from dental anesthesia may reduce marrow vascularity beyond recovery. This problem may be enhanced by the temporary nature of vasoconstriction because damaging free radicals (oxyradicals) are created in remarkable abundance in ischemic tissues when reperfused.⁶¹

This investigation appears to indicate that the great majority of Case 1 and Case 2 scenario patients suffered from intramedullary disease, but it must be remembered that patients were initially identified through a biopsy service, with the case-selection biases that implies. The majority of prosthetic patients, even those with pain, do not have biopsies of subpontic bone and were naturally excluded from this investigation. The retrospective nature of the study also did not allow experimental manipulation of investigative parameters.

The frequency and incidence of ischemic osteonecrosis of the jaws is unknown. It may be that mild ischemic changes are a "natural" part of the aging process, similar to a disease process like atherosclerosis, which becomes extremely common with increasing age. Enlow⁶² reported ischemic loss of osteocytes greater in the jaws of older monkeys when compared to younger monkeys. Graff-Radford⁶³ identified numerous small marrow "cavitations" in the jawbones of elderly human cadavers without apparent histories of facial pain, although he did not control for diseases known to be associated with ischemic osteonecrosis (Table 5). Oikarenin⁶³ discovered through an excellent cadaver investigation, that after 40 years of age the inferior alveolar artery showed an increasing degree of degenerative changes, both age changes and arteriosclerotic changes, in the form of narrowings and tortuosity, particularly for edentulous ridges.

Bone marrow is not uniformly perfused and this accentuates the blood flow dilemma.^64,65 Certain areas are more susceptible to ischemic changes than other areas in close proximity within the same bone. Normal marrow has been admixed with damaged marrow in ischemic osteonecrosis and a dentist must be careful to obtain adequate tissue for a diagnosis. This may be difficult because many patients have desiccated, hollow, medullary spaces, called cavitations, similar to empty spaces of traumatic (idiopathic, unicameral) bone cyst. It may be impossible to secure a sufficient tissue sample from such a case. Cavitations are critical diagnostic data because few diseases are capable of producing "air-filled" spaces in cancellous bone.

This preliminary investigation strongly suggested that intraosseous ischemia, infarction and low-grade inflammation were substantial explanations for at least some, and perhaps many, patients with chronic idiopathic facial pain and subpontic phantom pain. It additionally helped to explain cases of poor bone healing of extraction sites and offered an insight into cases of chronic facial pain initiated by routine restorative procedures. The limitations of the study suggest that more extensive, prospective, case-controlled studies are necessary. If additional investigations corroborate the results of this study, the therapy for idiopathic facial pain should focus on treatment of osseous or coagulation disorders rather than on neurological diseases of unknown etiology.^16,56

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Tables

Table 1: Causes of "idiopathic" chronic jawbone pain, excluding temporomandibular disorders and dental infections.^1-11,15

Table 2: Radiographic staging for ischemic osteonecrosis (applies predominantly to hip lesions and ends of long bones); patients at all stages may or may not have pain.^7,8,10

* bases on 14 patients with available lab values: 6 with thrombophilia, 4 with hyperfibrinolysis,
   4 with normal values
** bases on 9 patients who had undergone scintiscans

Figures

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